Psychoactive Drug Mechanisms -- Neurotransmitter.net

psychoactive drug mechanisms

-The information listed below is not intended to be interpreted as comprehensive. I have generally omitted the indirect effects of the drugs. Unidentified direct mechanisms of action may remain for a number of drugs; be aware that some receive much more research attention than others. Neurotransmitter.net does not advise anyone to consume any drug without the direction or supervision of a medical doctor. Any misuse or undirected use of any drug may lead to abuse or addiction, as discussed at prescription-drugrehab.org. If you can suggest important information that I may have left out, please feel free to contact me (Shawn Thomas). If you need a brief introduction to common terms used to describe the effects of drugs at receptors, see http://www.rsc.org/pdf/books/medicisc.pdf or http://www.anaesthetist.com/physiol/basics/receptor/receptor.htm. Information on endogenous neuroactive ligands and their receptors may be found at http://www.neurotransmitter.net/neurosignaling.html.

-Consider Futures of Palm Beach if you or a loved one are in need of inpatient addiction treatment.

-Information about FDA approved drugs has been moved to Neurotransmitter.net's Drug Reference for FDA Approved Psychiatric Drugs, Drug Reference for FDA Approved Opioids, Drug Reference for FDA Approved Antiepileptic Drugs, Drug Reference for General Anesthetic Drugs, andDrug Reference for FDA Approved Alzheimer's Disease Drugs

Confused by the terminology? Try searching The On-Line Medical Dictionary (OMD).

-- Absinthe --

The active ingredients in absinthe are alpha-thujone, beta-thujone, and ethanol. Alpha-thujone is active at the noncompetitive blocker sites of GABA-A receptors, which modulate chloride channels. Alpha-thujone is considered to be the primary active ingredient in wormwood oil (used to make absinthe) and is likely to be responsible for the toxic properties of absinthe. Beta-thujone is 2.3-fold less potent at GABA-A receptors than alpha-thujone, and it is therefore less toxic. See the entry for alcohol on this page for information about ethanol's apparent mechanisms of action.

Hold KM, Sirisoma NS, Ikeda T, Narahashi T, Casida JE.
Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification.
Proc Natl Acad Sci U S A 2000 Apr 11;97(8):3826-31 [Full Text]

Richard W. Olsen
Absinthe and gamma-aminobutyric acid receptors
PNAS 97: 4417-4418, April 2000. [Full Text]

-- Adrafinil --

Adrafinil is believed to function as a norepinephrine alpha-1 receptor agonist.

Milgram NW, Siwak CT, Gruet P, Atkinson P, Woehrle F, Callahan H.
Oral administration of adrafinil improves discrimination learning in aged beagle dogs.
Pharmacol Biochem Behav 2000 Jun;66(2):301-5 [Abstract]

-- Alcohol --

Ethyl alcohol, or ethanol, achieves its effects by altering the function of ligand- and voltage-gated ion channels. The sensitivity of these channels to ethanol is determined by their subtypes; an ion channel is typically composed of a combination of subunits that determines its subtype. Ethanol's biochemical and behavioral effects are primarily mediated by its positive modulation of GABA-A receptors. Ethanol also has inhibitory effects on glutamate-activated NMDA receptors and to a lesser degree, non-NMDA glutamate-activated receptors. Ethanol may positively affect the function of serotonin 5-HT3 receptors and neuronal nicotinic acetylcholine receptors. Glycine receptors have been found to be modulated by ethanol as well. Finally, voltage-gated ion channels, including voltage-gated calcium channels, may be inhibited by high concentrations of ethanol.

Suggestions have been made that ethanol's effects at GABA-A receptors are primarily mediated by indirect intracellular actions of the drug. A similar statement might apply to ethanol's activities at other receptor types; the complexity and range of ethanol's effects should not be underestimated. Many of the drug's effects may be mediated by the activation or inhibition of various protein kinase C (PKC) isoforms. The intracellular effects of ethanol are likely to depend on the type and biochemical makeup of the cells that it affects.

Some ethanol- containing beverages may also contain a number of other psychoactive substances. For example, whiskey can induce a greater sedative effect than ethanol alone. Certain components of whiskey such as ethyl phenylpropanoate can potentiate GABA-A receptor- mediated responses, and the degree of potentiation increases as whiskey ages.

Sanna E, Harris RA.
Recent developments in alcoholism:neuronal ion channels.
Recent Dev Alcohol 1993;11:169-86 [Abstract]

Crews FT, Morrow AL, Criswell H, Breese G.
Effects of ethanol on ion channels.
Int Rev Neurobiol. 1996;39:283-367. [Abstract]

Chester JA, Cunningham CL.
GABA(A) receptor modulation of the rewarding and aversive effects of ethanol.
Alcohol 2002 Apr;26(3):131-43 [Abstract]

Narahashi T, Aistrup GL, Marszalec W, Nagata K.
Neuronal nicotinic acetylcholine receptors: a new target site of ethanol.
Neurochem Int 1999 Aug;35(2):131-41 [Abstract]

Aguayo LG, Peoples RW, Yeh HH, Yevenes GE.
GABA(A) receptors as molecular sites of ethanol action. Direct or indirect actions?
Curr Top Med Chem 2002 Aug;2(8):869-85 [Abstract]

Hossain SJ, Aoshima H, Koda H, Kiso Y.
Potentiation of the ionotropic GABA receptor response by whiskey fragrance.
J Agric Food Chem. 2002 Nov 6;50(23):6828-34. [Abstract]

Koda H, Hossain SJ, Kiso Y, Aoshima H.
Aging of whiskey increases the potentiation of GABA(A) receptor response.
J Agric Food Chem. 2003 Aug 27;51(18):5238-44. [Abstract]

-- Alpha-ethyltryptamine --

Alpha-ethyltryptamine (AET) is a reversible MAO-A inhibitor. In addition, AET is a potentially neurotoxic drug that causes the release of monoamines such as serotonin from neurons.

Fredriksson A, Palomo T, Archer T.
Effects of MAO inhibitors upon MPTP mice chronically treated with suprathreshold doses of L-dopa.
Behav Pharmacol 2000 Nov;11(7-8):571-81 [Abstract]

Huang XM, Johnson MP, Nichols DE.
Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase).
Eur J Pharmacol 1991 Jul 23;200(1):187-90 [Abstract]

-- Alpha-methyltryptamine --

Alpha-methyltryptamine, a primary amine also known as AMT, is a non-hydrazine type monoamine oxidase (MAO) inhibitor. The drug inhibits MAO-A more potently than MAO-B, and it may also inhibit semicarbazide-sensitive amine oxidase (SSAO). MAO-A preferentially deaminates serotonin and norepinephrine, and it also non-selectively deaminates dopamine to a lesser degree. MAO-B primarily metabolizes dopamine, phenylethylamine, and various trace amines; however, a relatively small percentage of serotonin and norepinephrine may be deaminated by MAO-B in some regions of the brain.

Arai Y, Toyoshima Y, Kinemuchi H.
Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. II. Inhibition by alpha-methylated substrate-analogue monoamines, alpha-methyltryptamine, alpha-methylbenzylamine and two enantiomers of alpha-methylbenzylamine.
Jpn J Pharmacol 1986 Jun;41(2):191-7 [Abstract]

Feldman JM, Chapman B.
Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion.
Diabetologia 1975 Dec;11(6):487-94 [Abstract]

Fagervall I, Ross SB.
A and B forms of monoamine oxidase within the monoaminergic neurons of the rat brain.
J Neurochem 1986 Aug;47(2):569-76 [Abstract]

-- Amiflamine --

Amiflamine is a reversible MAO-A inhibitor.

Fredriksson A, Palomo T, Archer T.
Effects of MAO inhibitors upon MPTP mice chronically treated with suprathreshold doses of L-dopa.
Behav Pharmacol 2000 Nov;11(7-8):571-81 [Abstract]

-- Amanita muscaria --

Amanita muscaria is a hallucinogenic mushroom that contains two primary psychoactive constituents, muscimol and ibotenic acid. Muscimol is an agonist at GABA-A receptors and is the primary active component of the mushroom. Ibotenic acid activates all types of inhibitory glutamate receptors (IGluRs), although it may not readily cross the blood brain barrier. A. muscaria may also contain a small amount of muscarine, which is active at muscarinic acetylcholine receptors.

Erowid
Pharmacology of Amanita muscaria [Link]

Cleland TA.
Inhibitory glutamate receptor channels.
Mol Neurobiol 1996 Oct;13(2):97-136 [Abstract]

Krogsgaard-Larsen P, Frolund B, Liljefors T.
Specific GABAA agonists and partial agonists.
Chem Rec 2002;2(6):419-30 [Abstract]

--Atropine --

Atropine is a nonselective muscarinic acetylcholine receptor antagonist.

Kobayashi S, Ikeda K, Miyata K, Yamada T, Honda K.
A method for measurement of muscarinic receptor-mediated responses in dissociated single colon longitudinal smooth muscle cells.
J Pharmacol Toxicol Methods 2001 May-Jun;45(3):199-205 [Abstract]

-- Ayahuasca --

Ayahuasca works via the combined actions of N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids. DMT is a hallucinogenic drug that acts as a partial agonist at serotonin 5-HT2A and 5-HT2C receptors. The beta-carboline alkaloid components are believed to possess highly active reversible MAO-A inhibiting properties. The three main beta-carbolines present in ayahuasca are harmine, harmaline, and tetrahydroharmine (THH). Because MAO-A is known to cause the degradation of orally ingested DMT, the beta-carbolines found in ayahuasca allow the drug to become active when taken orally.

Yritia M, Riba J, Ortuno J, Ramirez A, Castillo A, Alfaro Y, de la Torre R, Barbanoj MJ.
Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca.
J Chromatogr B Analyt Technol Biomed Life Sci 2002 Nov 5;779(2):271-81 [Abstract]

McKenna DJ, Towers GH, Abbott F.
Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca.
J Ethnopharmacol 1984 Apr;10(2):195-223 [Abstract]

-- Baclofen --

Baclofen is an agonist at GABA-B receptors.

Zarrindast MR, Bakhsha A, Rostami P, Shafaghi B.
Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats.
J Psychopharmacol 2002 Dec;16(4):313-9 [Abstract]

-- Barbiturates and Benzodiazepines --

Barbiturates and benzodiazepines act at two different allosteric modulatory sites on gamma-aminobutyric acid type A (GABA-A) receptors. Because GABA-A receptors modulate chloride channels, barbiturates and benzodiazepines positively regulate the flow of chloride ions into neurons. The GABA-A receptor is a pentameric protein that may consist of a number of different combinations of subunits. The efficacy of these drugs at GABA-A receptors depends on the subunit compositions of the GABA-A receptor complexes that they bind to. The benzodiazepines have been found to bind to a subunit cleft on the GABA-A receptor surface located between the alpha and gamma subunits. Due to their lack of selectivity for receptor subtypes and increased efficacy, barbiturates are considered to be less safe than newer types of GABA-A modulatory drugs such as the benzodiazepines. Both drug types allosterically alter the shape of GABA-A receptors, which causes the receptors to exhibit a stronger affinity for GABA. Chloride channels in GABA-A receptor complexes exhibit at least three different open states that are characterized by their durations in milliseconds.

Barbiturates increase the relative frequency of the occurrence of the longest open state and decrease the frequency of the occurrence of the shorter open states, but benzodiazepines only increase the frequency that the channels will open into the shortest open state. It is also worthwhile to note that barbiturate abuse is quite prevalent in this country. Unlike benzodiazepines, barbiturates possess the ability to cause chloride channels in GABA-A receptor complexes to open in the absence of GABA. Some barbiturates may also affect other targets such as glycine channels, voltage-gated calcium channels, glutamate receptors, and nicotinic acetylcholine receptors; a few benzodiazepines might affect other targets as well. Drugs classified as benzodiazepines include alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), flurazepam, bromazepam, brotizolam, camazepam, clobazam, clotiazepam, cloxazolam, delorazepam, estazolam, ethyl loflazepate, fludiazepam, halazepam, haloxazolam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, oxazolam, pinazepam, prazepam, tetrazepam, and triazolam. Note that the drugs listed do not share the same selectivity and pharmacokinetic profile.

Sigel E.
Mapping of the benzodiazepine recognition site on GABA(A) receptors.
Curr Top Med Chem 2002 Aug;2(8):833-9 [Abstract]

Mehta AK, Ticku MK.
An update on GABAA receptors.
Brain Res Brain Res Rev 1999 Apr;29(2-3):196-217 [Abstract]

Hevers W, Luddens H.
The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.
Mol Neurobiol 1998 Aug;18(1):35-86 [Abstract]

Doble A.
New insights into the mechanism of action of hypnotics.
J Psychopharmacol 1999;13(4 Suppl 1):S11-20 [Abstract]

MacDonald RL, Rogers CJ, Twyman RE.
Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture.
J Physiol. 1989 Oct;417:483-500. [Abstract]

Neil Harrison, Wallace B. Mendelson and Harriet de Wit
Barbiturates
Psychopharmacology - The Fourth Generation of Progress [Full Text]

-- Benztropine --

Benztropine is an antagonist at all subtypes of muscarinic acetylcholine receptors. Benztropine inhibits voltage- gated sodium channels in a use- dependent manner; the drug preferentially binds to the channel pore in the inactivated state. The drug may also act as an antagonist at histamine H1 receptors. At higher concentrations, benztropine may act as an antagonist at nicotinic acetylcholine receptors.

Bolden C, Cusack B, Richelson E.
Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells.
J Pharmacol Exp Ther 1992 Feb;260(2):576-80 [Abstract]

Kuo, Chung-Chin, Huang, Ron-Chi, Lou, Bih-Show
Inhibition of Na+ Current by Diphenhydramine and Other Diphenyl Compounds: Molecular Determinants of Selective Binding to the Inactivated Channels
Mol Pharmacol 2000 57: 135-143 [Full Text]

McKearney JW.
Stimulant actions of histamine H1 antagonists on operant behavior in the squirrel monkey.
Psychopharmacology (Berl) 1982;77(2):156-8 [Abstract]

Gao ZG, Liu BY, Cui WY, Li LJ, Fan QH, Liu CG.
Anti-nicotinic properties of anticholinergic antiparkinson drugs.
J Pharm Pharmacol 1998 Nov;50(11):1299-305 [Abstract]

-- Betel Nut --

The principal active constituent of the betel nut, or Areca catechu, is arecoline. Arecoline is an agonist at M1, M2, M3, M4, and M5 muscarinic acetylcholine receptors. The sympathetic activities of arecoline are thought to be mediated by M2 receptors on the cell membranes of locus coeruleus neurons. Active constituents in Areca catechu also include arecaidin, arecaine, and choline; each of these affects acetylcholine-related systems as well.

Yang YR, Chang KC, Chen CL, Chiu TH.
Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor.
Chin J Physiol 2000 Mar 31;43(1):23-8 [Abstract]

Ghelardini C, Galeotti N, Lelli C, Bartolini A.
M1 receptor activation is a requirement for arecoline analgesia.
Farmaco 2001 May-Jul;56(5-7):383-5 [Abstract]

Okamoto H, Prestwich SA, Asai S, Unno T, Bolton TB, Komori S.
Muscarinic agonist potencies at three different effector systems linked to the M(2) or M(3) receptor in longitudinal smooth muscle of guinea-pig small intestine.
Br J Pharmacol 2002 Apr;135(7):1765-75 [Abstract]

McKinney M, Miller JH, Gibson VA, Nickelson L, Aksoy S.
Interactions of agonists with M2 and M4 muscarinic receptor subtypes mediating cyclic AMP inhibition.
Mol Pharmacol 1991 Dec;40(6):1014-22 [Abstract]

Spalding TA, Burstein ES, Brauner-Osborne H, Hill-Eubanks D, Brann MR.
Pharmacology of a constitutively active muscarinic receptor generated by random mutagenesis.
J Pharmacol Exp Ther 1995 Dec;275(3):1274-9 [Abstract]

-- Bethanechol --

Bethanechol acts as a full or partial agonist at muscarinic acetylcholine M1, M2, M3, M4, and possibly M5 type receptors.

Sharif NA, Williams GW, DeSantis LM.
Affinities of muscarinic drugs for [3H]N-methylscopolamine (NMS) and [3H]oxotremorine (OXO) binding to a mixture of M1-M4 muscarinic receptors: use of NMS/OXO-M ratios to group compounds into potential agonist, partial agonist, and antagonist classes.
Neurochem Res 1995 Jun;20(6):669-74 [Abstract]

McKinney M, Miller JH, Gibson VA, Nickelson L, Aksoy S.
Interactions of agonists with M2 and M4 muscarinic receptor subtypes mediating cyclic AMP inhibition.
Mol Pharmacol 1991 Dec;40(6):1014-22 [Abstract]

-- Bicuculline --

Bicuculline is a GABA-A receptor antagonist.White AM, Platt B.
Gamma-aminobutyric acid-induced calcium signalling in rat superior collicular neurones.
Neurosci Lett 2002 Dec 13;334(2):79-82 [Abstract]

-- Bromocriptine --

Bromocriptine is an agonist at dopamine D2, D3, and D4 receptors.

Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM.
Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.
Eur J Pharmacol 1995 Jun 23;290(1):29-36 [Abstract]

-- Brofaromine --

Brofaromine is a selective and reversible inhibitor of monoamine oxidase type A (MAO-A).

Gerardy J, Dresse A.
Regional action of brofaromine on rat brain MAO-A and MAO-B.
Prog Neuropsychopharmacol Biol Psychiatry 1998 Oct;22(7):1141-55 [Abstract]

-- Caffeine --

Caffeine, a methylxanthine, acts as a competitive antagonist at adenosine receptors. Four distinct types of adenosine receptors, A1, A2A, A2B, and A3, are currently known to exist. Caffeine's effects are primarily mediated by its inhibition of A1 and A2A type receptors. The drug is also a nonselective phosphodiesterase inhibitor; however, normal consumption of caffeine is not likely to induce this effect.

Fredholm, Bertil B., Battig, Karl, Holmen, Janet, Nehlig, Astrid, Zvartau, Edwin E.
Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use
Pharmacol Rev 1999 51: 83-133 [Full Text]

Fredholm, Bertil B., IJzerman, Adriaan P., Jacobson, Kenneth A., Klotz, Karl-Norbert, Linden, Joel
International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors
Pharmacol Rev 2001 53: 527-552 [Full Text]

Lindaman BA, Hinkhouse MM, Conklin JL, Cullen JJ.
The effect of phosphodiesterase inhibition on gallbladder motility in vitro.
J Surg Res 2002 Jun 15;105(2):102-8 [Abstract]

-- 2C-B --

4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a hallucinogen that may act as a partial agonist at serotonin 5-HT2A receptors, serotonin 5-HT2C receptors, and alpha-1-adrenoceptors. The drug may also bind to serotonin 5-HT1A and 5-HT1B receptors.

Lobos M, Borges Y, Gonzalez E, Cassels BK.
The action of the psychoactive drug 2C-B on isolated rat thoracic aorta.
Gen Pharmacol. 1992 Nov;23(6):1139-42. [Abstract]

Claudio Acuña-Castillo, Claudio Villalobos, Pablo R. Moya, Patricio Sáez, Bruce K. Cassels, and J. Pablo Huidobro-Toro
Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT2A and5-HT2C receptors
Br J Pharmacol 2002 136: 510-519. [Abstract]

Glennon RA, Titeler M, Lyon RA.
A preliminary investigation of the psychoactive agent 4-bromo-2,5-dimethoxyphenethylamine: a potential drug of abuse.
Pharmacol Biochem Behav. 1988 Jul;30(3):597-601. [Abstract]

-- Carbogen --

Carbogen is a mixture of 95% oxygen and 5% carbon dioxide.

Taylor NJ, Baddeley H, Goodchild KA, Powell ME, Thoumine M, Culver LA, Stirling JJ, Saunders MI, Hoskin PJ, Phillips H, Padhani AR, Griffiths JR.
BOLD MRI of human tumor oxygenation during carbogen breathing.
J Magn Reson Imaging 2001 Aug;14(2):156-63 [Abstract]

-- Cimoxatone --

Cimoxatone is a selective and reversible inhibitor of monoamine oxidase type A (MAO-A).

Delini-Stula A, Radeke E, Waldmeier PC.
Basic and clinical aspects of the activity of the new monoamine oxidase inhibitors.
Psychopharmacol Ser 1988;5:147-58 [Abstract]

-- Clonidine --

Clonidine is a partial agonist at norepinephrine alpha-2 receptors and an agonist at imidazoline I1 receptors. Clonidine has also been shown to exhibit weak agonist activity at norepinephrine alpha-1 receptors.

Piletz JE, Ordway GA, Zhu H, Duncan BJ, Halaris A.
Autoradiographic comparison of [3H]-clonidine binding to non-adrenergic sites and alpha(2)-adrenergic receptors in human brain.
Neuropsychopharmacology 2000 Dec;23(6):697-708 [Abstract]

Serban DN, Nechifor M, Slatineanu SM.
Implications of imidazolines and imidazoline receptors role at the vascular level.
Rev Med Chir Soc Med Nat Iasi. 2000 Oct-Dec;104(4):37-44. [Abstract]

Iwanaga S, Shibata O, Tsuda A, Hashimoto S, Makita T, Cho S, Sumikawa K.
The role of alpha1-adrenoceptors in the clonidine-induced contraction and relaxation of rat aorta.
Res Commun Mol Pathol Pharmacol 1998 Nov;102(2):137-47 [Abstract]

-- Cocaine --

Cocaine inhibits the reuptake of dopamine, serotonin, and norepinephrine into nerve terminals. In addition, cocaine is known to act as an agonist at sigma-1 receptors.

Ravna AW, Sylte I, Dahl SG.
Molecular mechanism of citalopram and cocaine interactions with neurotransmitter transporters.
J Pharmacol Exp Ther. 2003 Oct;307(1):34-41. Epub 2003 Aug 27. [Abstract]

Izenwasser S, Terry P, Heller B, Witkin JM, Katz JL.
Differential relationships among dopamine transporter affinities and stimulant potencies of various uptake inhibitors.
Eur J Pharmacol 1994 Oct 3;263(3):277-83 [Abstract]

Ramamoorthy, Sammanda, Blakely, Randy D.
Phosphorylation and Sequestration of Serotonin Transporters Differentially Modulated by Psychostimulants
Science 1999 285: 763-766 [Full Text]

Zhu, Meng-Yang, Shamburger, Susan, Li, Jing, Ordway, Gregory A.
Regulation of the Human Norepinephrine Transporter by Cocaine and Amphetamine
J Pharmacol Exp Ther 2000 295: 951-959 [Full Text]

Matsumoto RR, McCracken KA, Pouw B, Zhang Y, Bowen WD.
Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides.
Neuropharmacology. 2002 Jun;42(8):1043-55. [Abstract]

-- Dextromethorphan --

Dextromethorphan (DXM) exhibits relatively high affinity binding activity as a sigma-1 receptor agonist and serotonin reuptake inhibitor. DXM is also a noncompetitive NMDA receptor antagonist. The drug is four times more potent at NR1A/NR2A subunit-containing NMDA receptors than at NR1A/NR2B NMDA receptors. Furthermore, DXM exhibits a higher potency at NR1/NR2C receptors than at NR1/NR2A receptors. The active metabolite of DXM, dextrorphan, is a more potent noncompetitive NMDA antagonist and sigma-1 agonist than DXM. Dextrorphan and DXM also bind with low affinity to sigma-2 receptors. DXM and dextrorphan noncompetitively block alpha3beta4 neuronal nicotinic acetylcholine receptors; other nicotinic receptor subtypes may also be affected by these drugs. DXM is commonly found in over the counter cough remedies. The drug's antitussive effects are mediated by sigma-1 and serotonin 5-HT1A receptors; at therapeutically relevant concentrations, DXM is likely to cause the activation of 5-HT1A receptors indirectly via the inhibition of serotonin reuptake.

Kim HC, Bing G, Jhoo WK, Kim WK, Shin EJ, Im DH, Kang KS, Ko KH.
Metabolism to dextrorphan is not essential for dextromethorphan's anticonvulsant activity against kainate in mice.
Life Sci 2003 Jan 3;72(7):769-783 [Abstract]

Meoni P, Tortella FC, Bowery NG.
An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine.
Br J Pharmacol 1997 Apr;120(7):1255-62 [Abstract]

Avenet P, Leonardon J, Besnard F, Graham D, Depoortere H, Scatton B.
Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1A/NR2A and NR1A/NR2B receptors expressed in Xenopus oocytes.
Neurosci Lett 1997 Feb 21;223(2):133-6 [Abstract]

Monaghan, Daniel T., Larsen, Heidi
NR1 and NR2 Subunit Contributions to N-Methyl-D-aspartate Receptor Channel Blocker Pharmacology
J Pharmacol Exp Ther 1997 280: 614-620 [Full Text]

Chou YC, Liao JF, Chang WY, Lin MF, Chen CF.
Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan.
Brain Res 1999 Mar 13;821(2):516-9 [Abstract]

Zhou GZ, Musacchio JM.
Computer-assisted modeling of multiple dextromethorphan and sigma binding sites in guinea pig brain.
Eur J Pharmacol. 1991 Apr 25;206(4):261-9. [Abstract]

Hernandez, Susan C., Bertolino, Maria, Xiao, Yingxian, Pringle, Kenneth E., Caruso, Frank S., Kellar, Kenneth J.
Dextromethorphan and Its Metabolite Dextrorphan Block alpha 3beta 4 Neuronal Nicotinic Receptors
J Pharmacol Exp Ther 2000 293: 962-967 [Full Text]

Kamei J.
[Mechanisms of central antitussives]
Nippon Yakurigaku Zasshi 1998 Jun;111(6):345-55 [Abstract]

-- Dimenhydrinate --

Dimenhydrinate, also known as Dramamine, is a histamine H1 receptor antagonist. Some of its effects may be mediated by anticholinergic mechanisms as well.

Halpert AG, Olmstead MC, Beninger RJ.
Mechanisms and abuse liability of the anti-histamine dimenhydrinate.
Neurosci Biobehav Rev 2002 Jan;26(1):61-7 [Abstract]

-- Disulfiram --

Disulfiram is an irreversible inhibitor of aldehyde dehydrogenase. The drug is commonly used as an aversion therapy for recovering alcoholics.

Lipsky JJ, Shen ML, Naylor S.
Overview--in vitro inhibition of aldehyde dehydrogenase by disulfiram and metabolites.
Chem Biol Interact 2001 Jan 30;130-132(1-3):81-91 [Abstract]

-- DOB --

2,5-Dimethoxy-4-bromoamphetamine (DOB) is a phenylisopropylamine hallucinogen with partial agonist activity at serotonin 5-HT2A receptors. DOB is also an agonist at 5-HT2B and 5-HT2C receptors.

Arvanov VL, Liang X, Russo A, Wang RY.
LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex.
Eur J Neurosci 1999 Sep;11(9):3064-72 [Abstract]

Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ.
Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells.
Br J Pharmacol. 1999 Sep;128(1):13-20. [Abstract]

-- DOI --

1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is a full agonist at serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.

Porter RH, Benwell KR, Lamb H, Malcolm CS, Allen NH, Revell DF, Adams DR, Sheardown MJ.
Functional characterization of agonists at recombinant human 5-HT2A, 5-HT2B and 5-HT2C receptors in CHO-K1 cells.
Br J Pharmacol. 1999 Sep;128(1):13-20. [Abstract]

Nichols DE, Frescas S, Marona-Lewicka D, Huang X, Roth BL, Gudelsky GA, Nash JF.
1-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)-2-aminopropane: a potent serotonin 5-HT2A/2C agonist.
J Med Chem. 1994 Dec 9;37(25):4346-51. [Abstract]

-- DOM --

2,5-Dimethoxy-4-methylamphetamine (DOM) is a phenylisopropylamine hallucinogen that is an agonist at serotonin 5-HT2A and 5-HT2C receptors. DOM may also act as an agonist at 5-HT3 receptors.

Aulakh CS, Mazzola-Pomietto P, Hill JL, Murphy DL.
Role of various 5-HT receptor subtypes in mediating neuroendocrine effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats.
J Pharmacol Exp Ther 1994 Oct;271(1):143-8 [Abstract]

-- DMT --

N,N-dimethyltryptamine (DMT) is a potent hallucinogenic drug that acts as a partial agonist at serotonin 5-HT2A and 5-HT2C receptors. DMT's potency is primarily due to its activity at 5-HT2A receptors. DMT is also an agonist at TA1, a trace amine receptor.

Smith RL, Canton H, Barrett RJ, Sanders-Bush E.
Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.
Pharmacol Biochem Behav 1998 Nov;61(3):323-30 [Abstract]

McClue SJ, Brazell C, Stahl SM.
Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor.
Biol Psychiatry 1989 Jul;26(3):297-302 [Abstract]

Jacob MS, Presti DE.
Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.
Med Hypotheses. 2005;64(5):930-7.Med Hypotheses. 2005;64(5):930-7. [Abstract]

Bunzow, James R., Sonders, Mark S., Arttamangkul, Seksiri, Harrison, Laura M., Zhang, Ge, Quigley, Denise I., Darland, Tristan, Suchland, Katherine L., Pasumamula, Shailaja, Kennedy, James L., Olson, Susan B., Magenis, R. Ellen, Amara, Susan G., Grandy, David K.
Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor
Mol Pharmacol 2001 60: 1181-1188 [Full Text]

-- Entacapone --

Entacapone, a drug used to treat Parkinson's disease, is a peripheral catechol-O-methyltransferase (COMT) inhibitor. Entacapone is not an effective inhibitor of central COMT. The drug is used to increase the bioavailability of L-dopa by preventing its peripheral degradation.

Forsberg, Markus, Lehtonen, Marko, Heikkinen, Minna, Savolainen, Jouko, Jarvinen, Tomi, Mannisto, Pekka T.
Pharmacokinetics and Pharmacodynamics of Entacapone and Tolcapone after Acute and Repeated Administration: A Comparative Study in the Rat
J Pharmacol Exp Ther 2003 304: 498-506 [Full Text]

Brusa L, Pierantozzi M, Bassi A, Fedele E, Lunardi G, Giacomini P, Stanzione P.
Temporal administration of entacapone with slow release L-dopa: pharmacokinetic profile and clinical outcome.
Neurol Sci. 2004 Jun;25(2):53-6. [Abstract]

-- Ephedrine --

Ephedrine, an antiasthmatic drug, is a weak partial agonist at beta-1 and beta-2 adrenoceptors in humans. It also causes the release of norepinephrine.

Shannon JR, Gottesdiener K, Jordan J, Chen K, Flattery S, Larson PJ, Candelore MR, Gertz B, Robertson D, Sun M.
Acute effect of ephedrine on 24-h energy balance.
Clin Sci (Lond) 1999 May;96(5):483-91 [Abstract]

Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS.
Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.
Synapse 2001 Jan;39(1):32-41 [Abstract]

-- Flesinoxan --

Flesinoxan is a phenylpiperazine with agonist actions at serotonin 5-HT1A receptors and antagonist actions at alpha-1-adrenoceptors.

Chidlow G, Cupido A, Melena J, Osborne NN.
Flesinoxan, a 5-HT1A receptor agonist/alpha 1-adrenoceptor antagonist, lowers intraocular pressure in NZW rabbits.
Curr Eye Res 2001 Aug;23(2):144-53 [Abstract]

-- Flumazenil --

Flumazenil antagonizes the effects of benzodiazepines at GABA-A receptors.

Zedkova L, Rauw GA, Baker GB, Coupland NJ.
A rapid high-pressure liquid chromatographic procedure for determination of flumazenil in plasma.
J Pharmacol Toxicol Methods 2001 Jul-Aug;46(1):57-60 [Abstract]

-- Gamma-hydroxybutyrate --

Gamma-hydroxybutyrate (GHB) is a naturally occuring metabolite of GABA that acts at GHB-specific, G protein-coupled presynaptic receptors. GHB is also a weak partial agonist at GABA-B receptors.

Snead, O. Carter, III
Evidence for a G Protein-Coupled {gamma}-Hydroxybutyric Acid Receptor
J Neurochem 2000 75: 1986-1996 [Full Text]

Lingenhoehl K, Brom R, Heid J, Beck P, Froestl W, Kaupmann K, Bettler B, Mosbacher J.
Gamma-hydroxybutyrate is a weak agonist at recombinant GABA(B) receptors.
Neuropharmacology 1999 Nov;38(11):1667-73 [Abstract]

-- Heroin --

Heroin, also known as diacetylmorphine, is an agonist at mu, delta, and kappa opioid receptors. Heroin metabolites such as 6-monoacetylmorphine, morphine, morphine-6-glucuronide, and morphine-3-glucuronide are also likely to contribute to the drug's effects.

Rady, Jodie J., Elmer, Gregory I., Fujimoto, James M.
Opioid Receptor Selectivity of Heroin Given Intracerebroventricularly Differs in Six Strains of Inbred Mice
J Pharmacol Exp Ther 1999 288: 438-445 [Full Text]

Rady, Jodie J., Holmes, Blythe B., Portoghese, Philip S., Fujimoto, James M.
Morphine Tolerance in Mice Changes Response of Heroin from {micro} to {delta} Opioid Receptors
Proc Soc Exp Biol Med 2000 224: 93-101 [Full Text]

Martin, Thomas J., Kim, Susy A., Cannon, David G., Sizemore, Glen M., Bian, Di, Porreca, Frank, Smith, James E.
Antagonism of delta 2-Opioid Receptors by Naltrindole-5'-isothiocyanate Attenuates Heroin Self-Administration but Not Antinociception in Rats
J Pharmacol Exp Ther 2000 294: 975-982 [Full Text]

Platt, Donna M., Rowlett, James K., Spealman, Roger D.
Discriminative Stimulus Effects of Intravenous Heroin and Its Metabolites in Rhesus Monkeys: Opioid and Dopaminergic Mechanisms
J Pharmacol Exp Ther 2001 299: 760-767 [Full Text]

-- Idazoxan --

Idozoxan is an antagonist at alpha-2-adrenoceptors. In addition, the drug also binds to imidazoline I(1) and I(2) receptors.

Ruiz J, Barinagarrementeria G, Martin-Gomez JI, Callado LF, Meana JJ.
Characterization of [(3)H]idazoxan binding sites on human platelets.
Platelets 2002 Jun;13(4):241-6 [Abstract]

-- LSD --

D-lysergic acid diethylamide (LSD) is a hallucinogenic drug due to its activity as a partial agonist at serotonin 5-HT2A receptors. LSD also binds to serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5, 5-HT6, 5-HT7, dopamine D1 and D2, and alpha-1 and alpha-2 adrenergic receptors. The drug's precise effects and binding affinities at the majority of these receptors are not well known. LSD also exhibits agonist activity at a rat trace amine receptor that is known to exist in humans.

Arvanov VL, Liang X, Russo A, Wang RY.
LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex.
Eur J Neurosci 1999 Sep;11(9):3064-72 [Abstract]

Bunzow, James R., Sonders, Mark S., Arttamangkul, Seksiri, Harrison, Laura M., Zhang, Ge, Quigley, Denise I., Darland, Tristan, Suchland, Katherine L., Pasumamula, Shailaja, Kennedy, James L., Olson, Susan B., Magenis, R. Ellen, Amara, Susan G., Grandy, David K.
Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor
Mol Pharmacol 2001 60: 1181-1188 [Full Text]

-- Marijuana --

The primary psychoactive constituent of marijuana, Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), is an agonist at CB1 and CB2 cannabinoid receptors. CB1 receptors are located primarily in the brain, while CB2 receptors are found primarily in the periphery. Additional cannabinoid receptors not affected by Cannabis sativa (marijuana) may also exist.

Wiley JL, Martin BR.
Cannabinoid pharmacology: implications for additional cannabinoid receptor subtypes.
Chem Phys Lipids 2002 Dec;121(1-2):57-63 [Abstract]

-- Mazindol --

Mazindol is a potent inhibitor of dopamine and norepinephrine transporters.

Tatsumi M, Groshan K, Blakely RD, Richelson E.
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
Eur J Pharmacol. 1997 Dec 11; 340(2-3): 249-58. [Abstract]

-- MDMA --

3,4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," achieves its effects primarily by indirectly causing the release of serotonin from neuron terminals; the drug also moderately affects norepinephrine and, to a lesser degree, dopamine release. After entering the serotonin transporter, MDMA has been shown to increase the activity of protein kinase C (PKC) in serotonergic nerve terminals; MDMA- activated PKC is likely to be responsible for the efflux of serotonin from serotonin transporters at plasma membranes. Similarly, PKC translocated by MDMA is likely to cause a reduction of the inward transport at serotonin transporters; recent reports have concluded that the inward and outward transport mechanisms of monoamine transporters are independently modulated. PKC activators are also known to internalize cell-surface serotonin transporters; the degree to which this effect causes a decrease in inward transport is difficult to determine. In addition to this effect, MDMA may also inhibit serotonin and norepinephrine reuptake by binding directly to the transporters, but this effect may occur only at higher doses of the drug.

Based on a recent description of amphetamine- induced increases in PKC activity, it is possible that MDMA- induced increases in phospholipase C activity may mediate its effects on PKC. The increase in extracellular serotonin caused by MDMA- induced presynaptic PKC activation and serotonin transporter inhibition may also contribute to postsynaptic PKC activation via serotonin 5-HT2 type receptors. MDMA- mediated increases in extracellular dopamine and norepinephrine levels are also likely to be mediated by PKC activation and transporter inhibition, but the drug is significantly more likely to be transported through serotonergic transporters than through dopaminergic or noradrenergic transporters; MDMA may enter dopamine terminals primarily through diffusion. The possibility also exists that MDMA- activated PKC could potentiate the release of monoamines through mechanisms not involving monoaminergic transporters. The effects of increased extracellular serotonin at postsynaptic serotonergic receptors are also likely to contribute to the release of other neurotransmitters. MDMA's vesicle-depleting effect is likely to represent the rate-limiting step in the monoamine efflux induced by the drug. MDMA redistributes neurotransmitters such as dopamine and serotonin from vesicles to the cytoplasm through two different mechanisms. First, the inhibitory effect of the drug on vesicular monoamine transporter-2 (VMAT-2) may inhibit monoamine uptake into vesicles. Second, MDMA may decrease VMAT-2 activity by reducing the transmembrane pH difference that drives amine uptake. Both mechanisms are likely to be involved in the process. The weak inhibition of MAO-A by the drug may also contribute to MDMA- induced increases in the monoamines available for efflux from serotonergic and dopaminergic terminals. Finally, MDMA exhibits agonist activity at TA1, a trace amine receptor. To learn more about MDMA- mediated effects and neurotoxicity, click here.

G Rudnick, and SC Wall
The Molecular Mechanism of "Ecstasy" [3,4-Methylenedioxy-Methamphetamine (MDMA)]: Serotonin Transporters are Targets for MDMA-Induced Serotonin Release
PNAS 89: 1817-1821, 1992. [Abstract/Full Text]

Fitzgerald JL, Reid JJ.
Effects of methylenedioxymethamphetamine on the release of monoamines from rat brain slices.
Eur J Pharmacol 1990 Nov 27;191(2):217-20 [Abstract]

Kramer HK, Poblete JC, Azmitia EC.
Characterization of the translocation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA/ecstasy) in synaptosomes: evidence for a presynaptic localization involving the serotonin transporter (SERT).
Neuropsychopharmacology 1998 Oct;19(4):265-77 [Abstract]

Sitte, Harald H., Hiptmair, Birgit, Zwach, Julia, Pifl, Christian, Singer, Ernst A., Scholze, Petra
Quantitative Analysis of Inward and Outward Transport Rates in Cells Stably Expressing the Cloned Human Serotonin Transporter: Inconsistencies with the Hypothesis of Facilitated Exchange Diffusion
Mol Pharmacol 2001 59: 1129-1137 [Full Text]

Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI.
The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
Pharmacol Rev. 2003 Sep;55(3):463-508. Epub 2003 Jul 17. [Abstract]

Giambalvo CT.
Mechanisms underlying the effects of amphetamine on particulate PKC activity.
Synapse. 2004 Feb;51(2):128-39. [Abstract]

Hansen, J. Paul, Riddle, Evan L., Sandoval, Veronica, Brown, Jeffrey M., Gibb, James W., Hanson, Glen R., Fleckenstein, Annette E.
Methylenedioxymethamphetamine Decreases Plasmalemmal and Vesicular Dopamine Transport: Mechanisms and Implications for Neurotoxicity
J Pharmacol Exp Ther 2002 300: 1093-1100 [Full Text]

Sammanda Ramamoorthy, Elena Giovanetti, Yan Qian, and Randy D. Blakely
Phosphorylation and Regulation of Antidepressant-sensitive Serotonin Transporters
J. Biol. Chem. 273: 2458-2466, 1998. [Full Text]

Schuldiner, S, Steiner-Mordoch, S, Yelin, R, Wall, SC, Rudnick, G
Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters
Mol Pharmacol 1993 44: 1227-1231 [Abstract]

Leonardi ET, Azmitia EC.
MDMA (ecstasy) inhibition of MAO type A and type B: comparisons with fenfluramine and fluoxetine (Prozac).
Neuropsychopharmacology. 1994 Jul;10(4):231-8. [Abstract]

Bunzow, James R., Sonders, Mark S., Arttamangkul, Seksiri, Harrison, Laura M., Zhang, Ge, Quigley, Denise I., Darland, Tristan, Suchland, Katherine L., Pasumamula, Shailaja, Kennedy, James L., Olson, Susan B., Magenis, R. Ellen, Amara, Susan G., Grandy, David K.
Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor
Mol Pharmacol 2001 60: 1181-1188 [Full Text]

-- 5-MeO-DMT --

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a hallucinogenic drug that acts nonselectively at serotonin receptors. 5-MeO-DMT binds to 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, and presumably other types of serotonin receptors. The hallucinogenic effects of the drug are due to its actions at 5-HT2A receptors in the brain. When taken as an inebriant by South American shamans, 5-MeO-DMT is typically combined with monoamine-oxidase-inhibiting beta-carbolines to potentiate the effects of the drug. Along with bufotenin, 5-MeO-DMT is present in the venom of a species of toad known as Bufo alvarius.

Winter JC, Filipink RA, Timineri D, Helsley SE, Rabin RA.
The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors.
Pharmacol Biochem Behav 2000 Jan 1;65(1):75-82 [Abstract]

Cardenas CG, Del Mar LP, Cooper BY, Scroggs RS.
5HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons.
J Neurosci 1997 Oct 1;17(19):7181-9 [Abstract]

Ott J.
Pharmepena-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.
J Psychoactive Drugs 2001 Oct-Dec;33(4):403-7 [Abstract]

-- Mescaline --

Mescaline, the principal psychoactive constituent of peyote and some other types of cacti, is a hallucinogen due to its partial agonist activity at serotonin 5-HT2A receptors. Mescaline is also an agonist at serotonin 5-HT2C receptors.

Aghajanian GK, Marek GJ.
Serotonin and hallucinogens.
Neuropsychopharmacology 1999 Aug;21(2 Suppl):16S-23S [Abstract]

Newton RA, Phipps SL, Flanigan TP, Newberry NR, Carey JE, Kumar C, McDonald B, Chen C, Elliott JM.
Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.
J Neurochem 1996 Dec;67(6):2521-31 [Abstract]

-- Moclobemide --

Moclobemide is a selective and reversible inhibitor of monoamine oxidase type A (MAO-A).

Fulton B, Benfield P.
Moclobemide. An update of its pharmacological properties and therapeutic use.
Drugs 1996 Sep;52(3):450-74 [Abstract]

-- Modafinil --

Modafinil (Provigil) is an agonist at alpha-1-adrenoceptors. The drug also inhibits dopamine reuptake transporters.

Duteil J, Rambert FA, Pessonnier J, Hermant JF, Gombert R, Assous E.
Central alpha 1-adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals.
Eur J Pharmacol. 1990 May 3;180(1):49-58. [Abstract]

Stone EA, Cotecchia S, Lin Y, Quartermain D.
Role of brain alpha 1B-adrenoceptors in modafinil-induced behavioral activity.
Synapse. 2002 Dec 15;46(4):269-70. [Abstract]

Nishino S, Mao J, Sampathkumaran R, Shelton J.
Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants.
Sleep Res Online. 1998;1(1):49-61. [Abstract]

-- Naltrexone --

Naltrexone is an antagonist at mu, delta, kappa, and epsilon opioid receptors.

Metzger TG, Paterlini MG, Ferguson DM, Portoghese PS.
Investigation of the selectivity of oxymorphone- and naltrexone-derived ligands via site-directed mutagenesis of opioid receptors: exploring the "address" recognition locus.
J Med Chem. 2001 Mar 15; 44(6): 857-62. [Abstract]

Giordano AL, Nock B, Cicero TJ.
Antagonist-induced up-regulation of the putative epsilon opioid receptor in rat brain: comparison with kappa, mu and delta opioid receptors.
J Pharmacol Exp Ther. 1990 Nov; 255(2): 536-40. [Abstract]

-- Naltrindole --

Naltrindole is a selective delta opioid receptor antagonist.

Rogers H, Hayes AG, Birch PJ, Traynor JR, Lawrence AJ.
The selectivity of the opioid antagonist, naltrindole, for delta-opioid receptors.
J Pharm Pharmacol. 1990 May; 42(5): 358-9. [Abstract]

Williams KL, Ko MC, Rice KC, Woods JH.
Effect of opioid receptor antagonists on hypothalamic-pituitary-adrenal activity in rhesus monkeys.
Psychoneuroendocrinology. 2003 May; 28(4): 513-28. [Abstract]

-- Nicotine --

Nicotine is a nonselective agonist at nicotinic acetylcholine receptors.

Tobacco Advisory Group of the Royal College of Physicians
Physical and pharmacological effects of nicotine in Nicotine Addiction in Britain. 2001.

-- Nimodipine --

Nimodipine is a selective blocker of L-type calcium channels.

van Luijtelaar G, Wiaderna D, Elants C, Scheenen W.
Opposite effects of T- and L-type Ca(2+) channels blockers in generalized absence epilepsy.
Eur J Pharmacol 2000 Oct 20;406(3):381-9 [Abstract]

-- Nor-binaltorphimine --

Nor-binaltorphimine is a selective kappa opioid receptor antagonist.

Hjorth SA, Thirstrup K, Grandy DK, Schwartz TW.
Analysis of selective binding epitopes for the kappa-opioid receptor antagonist nor-binaltorphimine.
Mol Pharmacol. 1995 Jun; 47(6): 1089-94. [Abstract]

-- PCP --

PCP, also known as phencyclidine, is a noncompetitive NMDA antagonist with equally potent activity at NR1A/NR2B and NR1A/NR2A subunit containing NMDA receptors. Some studies have suggested that PCP is an agonist at serotonin 5-HT2A receptors; in addition, PCP and its major metabolite may inhibit the serotonin transporter. PCP may also inhibit the dopamine transporter and act as a partial agonist at dopamine D2 receptors. In addition, PCP is a noncompetitive inhibitor of several subtypes of nicotinic acetylcholine receptors. It is worth noting that controversy surrounds the identification of PCP's non-NMDA binding sites.

Avenet P, Leonardon J, Besnard F, Graham D, Depoortere H, Scatton B.
Antagonist properties of eliprodil and other NMDA receptor antagonists at rat NR1A/NR2A and NR1A/NR2B receptors expressed in Xenopus oocytes.
Neurosci Lett 1997 Feb 21;223(2):133-6 [Abstract]

Gerhardt, GA, Pang, K, Rose, GM
In vivo electrochemical demonstration of the presynaptic actions of phencyclidine in rat caudate nucleus
J Pharmacol Exp Ther 1987 241: 714-721 [Abstract]

Kapur S, Seeman P.
NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia.
Mol Psychiatry. 2002;7(8):837-44. [Abstract]

Hori T, Suzuki T, Baba A, Abe S, Yamamoto T, Moroji T, Shiraishi H.
Effects of phencyclidine metabolites on serotonin uptake in rat brain.
Neurosci Lett. 1996 May 17;209(3):153-6. [Abstract]

Kuhar MJ, Boja JW, Cone EJ.
Phencyclidine binding to striatal cocaine receptors.
Neuropharmacology 1990 Mar;29(3):295-7 [Abstract]

Eaton MJ, Labarca C, Eterovic VA.
M2 mutations of the nicotinic acetylcholine receptor increase the potency of the non-competitive inhibitor phencyclidine.
J Neurosci Res 2000 Jul 1;61(1):44-51 [Abstract]

Fryer, John D., Lukas, Ronald J.
Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine
J Pharmacol Exp Ther 1999 288: 88-92 [Full Text]

-- Pramipexole --

Pramipexole (Mirapex) is an agonist at dopamine D2, D3, and D4 receptors; the drug is significantly more active at D3 receptors. Pramipexole is used in the treatment of Parkinson's disease.

Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM.
Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors.
Eur J Pharmacol 1995 Jun 23;290(1):29-36 [Abstract]

-- Prazosin --

Prazosin is an antihypertensive drug with inverse agonist properties at alpha-1A, alpha-1B, and alpha-1D adrenoceptors.

McCune DF, Edelmann SE, Olges JR, Post GR, Waldrop BA, Waugh DJ, Perez DM, Piascik MT.
Regulation of the cellular localization and signaling properties of the alpha(1B)- and alpha(1D)-adrenoceptors by agonists and inverse agonists.
Mol Pharmacol. 2000 Apr; 57(4): 659-66. [Abstract]

Hein P, Goepel M, Cotecchia S, Michel MC.
A quantitative analysis of antagonism and inverse agonism at wild-type and constitutively active hamster alpha1B-adrenoceptors.
Naunyn Schmiedebergs Arch Pharmacol. 2001 Jan; 363(1): 34-9. [Abstract]

Zhu J, Taniguchi T, Takauji R, Suzuki F, Tanaka T, Muramatsu I.
Inverse agonism and neutral antagonism at a constitutively active alpha-1a adrenoceptor.
Br J Pharmacol. 2000 Oct; 131(3): 546-52. [Abstract]

-- Psilocybin --

Psilocybin, found in several species of psychoactive mushrooms, is known to exhibit agonist activity at serotonin 5-HT2A and 5-HT1A receptors.

Vollenweider FX, Vontobel P, Hell D, Leenders KL.
5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man--a PET study with [11C]raclopride.
Neuropsychopharmacology 1999 May;20(5):424-33 [Abstract]

-- Rasagaline --

Rasagiline is a potent and selective irreversible MAO-B inhibitor.

Kupsch A.
Rasagiline. Teva Pharmaceutical.
Curr Opin Investig Drugs 2002 May;3(5):794-7 [Abstract]

-- Reboxetine --

Reboxetine, an antidepressant marketed as Edronax, is a norepinephrine reuptake inhibitor. Evidence suggests that reboxetine may also noncompetitively inhibit some subtypes of nicotinic acetylcholine receptors.

Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, Paykel E, Versiani M, Racagni G.
The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.
Eur Neuropsychopharmacol 2002 Oct;12(5):461-75 [Abstract]

Miller, Dennis K., Wong, Erik H. F., Chesnut, M. Dathan, Dwoskin, Linda P.
Reboxetine: Functional Inhibition of Monoamine Transporters and Nicotinic Acetylcholine Receptors
J Pharmacol Exp Ther 2002 302: 687-695 [Abstract]

-- Ropinirole --

Ropinirole (Requip) is an agonist at dopamine D2, D3, and D4 receptors. The drug is significantly more active at D3 receptors; it is at least 10-fold selective for D3 receptors over D2 or D4 receptors. Ropinirole is used in the treatment of Parkinson's disease.

Coldwell MC, Boyfield I, Brown T, Hagan JJ, Middlemiss DN.
Comparison of the functional potencies of ropinirole and other dopamine receptor agonists at human D2(long), D3 and D4.4 receptors expressed in Chinese hamster ovary cells.
Br J Pharmacol. 1999 Aug;127(7):1696-702. [Abstract]

Reavill C, Boyfield I, Coldwell M, Nelson P.
Comparative pharmacological study of ropinirole (SKF-101468) and its metabolites in rats.
J Pharm Pharmacol. 2000 Sep;52(9):1129-35. [Abstract]

-- Salvinorin A --

Salvinorin A, the primary active constituent in the hallucinogenic plant Salvia divinorum, is a selective kappa opioid receptor agonist. Recent unpublished research by Bryan L. Roth and Richard B. Rothman suggests that Salvinorin A is selective for the kappa1 opioid receptor subtype.

Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB.
Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
Proc Natl Acad Sci U S A 2002 Sep 3;99(18):11934-9 [Abstract]

-- Selegiline --

Selegiline ( (-)Deprenyl ) is an irreversible inhibitor of monoamine oxidase-B (MAO-B) at clinically relevant dosage levels. At higher concentrations, selegiline also acts as an MAO-A inhibitor. Although selegiline weakly inhibits the reuptake of dopamine and norepinephrine, the drug's primary metabolite, l-methamphetamine, is a more potent inhibitor of dopamine and norepinephrine transporters.

Antoniades C, Carageorgiou H, Tsakiris S.
Effects of (-)deprenyl (selegiline) on acetylcholinesterase and Na(+),K(+)-ATPase activities in adult rat whole brain.
Pharmacol Res 2002 Aug;46(2):165-9 [Abstract]

Kim EM, Chung HS, Lee KJ, Kim HJ.
Determination of enantiomeric metabolites of l-deprenyl, d-methamphetamine, and racemic methamphetamine in urine by capillary electrophoresis: comparison of deprenyl use and methamphetamine use.
J Anal Toxicol 2000 May-Jun;24(4):238-44 [Abstract]

Magyar K, Szende B, Lengyel J, Tarczali J, Szatmary I.
The neuroprotective and neuronal rescue effects of (-)-deprenyl.
J Neural Transm Suppl 1998;52:109-23 [Abstract]

-- Tolcapone --

Tolcapone (Tasmar), a drug used to treat Parkinson's disease, is a catechol-O-methyltransferase (COMT) inhibitor.

Forsberg, Markus, Lehtonen, Marko, Heikkinen, Minna, Savolainen, Jouko, Jarvinen, Tomi, Mannisto, Pekka T.
Pharmacokinetics and Pharmacodynamics of Entacapone and Tolcapone after Acute and Repeated Administration: A Comparative Study in the Rat
J Pharmacol Exp Ther 2003 304: 498-506 [Full Text]

-- Verapamil --

Verapamil, a phenylalkylamine, inhibits L-type voltage-gated calcium channels and HERG potassium channels in a frequency-dependent and use-dependent manner. The drug also inhibits cardiac type K(ATP) channels by increasing the amount of time that they spend in the closed state.

Nawrath H, Wegener JW.
Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels.
Naunyn Schmiedebergs Arch Pharmacol. 1997 Jan;355(1):79-86. [Abstract]

Shetuan Zhang, Zhengfeng Zhou, Qiuming Gong, Jonathan C. Makielski, and Craig T. January
Mechanism of Block and Identification of the Verapamil Binding Domain to HERG Potassium Channels
Circ. Res. 84: 989-998 [Full Text]

Ninomiya T, Takano M, Haruna T, Kono Y, Horie M.
Verapamil, a Ca2+ entry blocker, targets the pore-forming subunit of cardiac type KATP channel (Kir6.2).
J Cardiovasc Pharmacol. 2003 Aug;42(2):161-8. [Abstract]

-- Vigabatrin --

Vigabatrin (gamma-vinyl GABA) is an irreversible inhibitor of the enzyme GABA transaminase. This action effectively increases extracellular levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

Gardner EL, Schiffer WK, Horan BA, Highfield D, Dewey SL, Brodie JD, Ashby CR Jr.
Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats.
Synapse 2002 Dec 15;46(4):240-50 [Abstract]

->Back to Home<-