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Muscarinic antagonist

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Drug that binds to but does not activate muscarinic cholinergic receptors

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Muscarinic acetylcholine receptor antagonist
Drug class
Skeletal formula ofscopolamine, a nonselective antagonist of the muscarinic receptors
Class identifiers
Synonyms	Muscarinic acetylcholine receptor antagonist; Antimuscarinic; Anti-muscarinic; mACh antagonist; mAChR antagonist; Muscarinic antagonist; Antimuscarinic agent; Antimuscarinic drug; Antimuscarinic medication
Use	Allergies,asthma,atrial fibrillation withbradycardia,^[1]motion sickness,Parkinson's disease, etc.
ATC code	V
Biological target	Muscarinic acetylcholine receptors
External links
MeSH	D018727
Legal status
In Wikidata

Amuscarinic acetylcholine receptor antagonist, also simply known as amuscarinic antagonist or as anantimuscarinic agent, is a type ofanticholinergic drug that blocks the activity of themuscarinic acetylcholine receptors (mAChRs). The muscarinic receptors are proteins involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring. Notably, muscarinic antagonists reduce the activation of theparasympathetic nervous system. The normal function of the parasympathetic system is often summarised as "rest-and-digest", and includes slowing of the heart, an increased rate of digestion,narrowing of the airways, promotion of urination, and sexual arousal. Muscarinic antagonists counter this parasympathetic "rest-and-digest" response, and also work elsewhere in both thecentral andperipheral nervous systems.

Drugs with muscarinic antagonist activity are widely used in medicine, in the treatment oflow heart rate,overactive bladder, respiratory problems such asasthma andchronic obstructive pulmonary disease (COPD). A number of other drugs, such asantipsychotics and thetricyclic family of antidepressants, have incidental muscarinic antagonist activity which can cause unwanted side effects such asdifficulty urinating, dry mouth and skin, andconstipation.

Acetylcholine (often abbreviatedACh) is a neurotransmitter whose receptors are proteins found insynapses and other cell membranes. Besides responding to their primary neurochemical, neurotransmitter receptors can be sensitive to a variety of other molecules. Acetylcholine receptors are classified into two groups based on this:

muscarinic, which respond tomuscarine
nicotinic, which respond tonicotine

Most muscarinic receptor antagonists are synthetic chemicals; however, the two most commonly used anticholinergics,scopolamine andatropine, arebelladonna alkaloids, and are naturally extracted from plants such asAtropa belladonna, commonly known asdeadly nightshade. The name "belladonna", Italian for "beautiful woman", is thought to derive from one of the antimuscarinic effects of these alkaloids, having been put into use by women for the cosmetic purpose of promoting dilation of thepupils.^[2]

Muscarinic antagonist effects andmuscarinic agonist effects counterbalance each other forhomeostasis.

Certain muscarinic antagonists can be classified into either long-acting muscarinic receptor antagonists (LAMAs) or short-acting muscarinic receptor antagonists (SAMAs), depending on when maximum effect occurs and for how long the effect persists.^[3]

Effects

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Scopolamine andatropine have similar effects on theperipheral nervous system. However, scopolamine has greater effects on thecentral nervous system (CNS) than atropine due to its ability to cross theblood–brain barrier.^[4] At higher-than-therapeutic doses, atropine and scopolamine cause CNS depression characterized by amnesia, fatigue, and reduction inrapid eye movement sleep. Scopolamine (Hyoscine) hasanti-emetic activity and is, therefore, used to treatmotion sickness.

Antimuscarinics are also used as anti-parkinsonian drugs. Inparkinsonism, there is imbalance between levels ofacetylcholine anddopamine in the brain, involving both increased levels of acetylcholine and degeneration ofdopaminergic pathways (nigrostriatal pathway). Thus, in parkinsonism there is decreased level of dopaminergic activity. One method of balancing the neurotransmitters is through blocking central cholinergic activity using muscarinic receptor antagonists.

Atropine acts on theM2 receptors of the heart and antagonizes the activity of acetylcholine. It causestachycardia by blocking vagal effects on thesinoatrial node. Acetylcholine hyperpolarizes the sinoatrial node; this is overcome by MRAs, and thus they increase the heart rate. If atropine is given by intramuscular or subcutaneous injection, it causes initialbradycardia. This is because when administered intramuscularly or subcutaneously atropine acts on presynapticM1 receptors (autoreceptors). Uptake of acetylcholine inaxoplasm is prevented and the presynaptic nerve releases more acetylcholine into thesynapse, which initially causes bradycardia.

In theatrioventricular node, theresting potential is lowered, which facilitates conduction. This is seen as a shortened PR-interval on anelectrocardiogram. It^{[clarification needed]} has an opposite effect onblood pressure. Tachycardia and stimulation of thevasomotor center causes an increase in blood pressure. But, due to feedback regulation of the vasomotor center, there is a fall in blood pressure due tovasodilation.

Important^[5] muscarinic antagonists includeatropine,hyoscyamine,hyoscine butylbromide andhydrobromide,ipratropium,tropicamide,cyclopentolate,pirenzepine andscopolamine.

Muscarinic antagonists such asipratropium bromide can also be effective in treatingasthma, sinceacetylcholine is known to causesmooth muscle contraction, especially in thebronchi.

Further information:Cholinergic crisis § Treatment

Comparison table

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This sectionis inlist format but may read better asprose. You can help byconverting this section, if appropriate.Editing help is available.(March 2024)

Overview

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Substance	Selectivity	Clinical use	Adverse effects	Notes	Trade names
Atropine (D/L-Hyoscyamine)	NS	Duringanesthesia^[5]^[6] Antidote toanticholinesterase poisoning^[5] Atrial fibrillation withbradycardia^[1]^[5] Antispasmodic in gastrointestinalhypermotility^[5]	UR^[5] xerostomia^[5] blurred vision^[5]	CD [5]	Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S and Neoquess
Atropine methonitrate	NS	antispasmodic in gastrointestinalhypermotility^[5]		Blocks transmission inganglia.^[5] Lacks CNS effects^[7]
Aclidinium bromide	Selective^{[clarification needed]}	Bronchospasm COPD		Long acting antagonist	Tudorza
Benztropine	M1-selective	PD EPS caused by typical and atypicalantipsychotics		Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.	Cogentin
Cyclopentolate	NS	producemydriasis andcycloplegia in diagnostics^[5]	may causeocular hypertension^[5]	Short acting,CD [5]
Diphenhydramine	NS	for EPS from typical and atypicalantipsychotic medications antihistamine sleep aid PD management ofasthma symptoms antiemetic	sedation dry mouth constipation UR	Acts in the central nervous system, blood vessels and smooth muscle tissues	Benadryl,Nytol
Doxylamine	NS	antihistamine^[8] antiemetic sleep aid	dizziness dry mouth		Unisom
Dimenhydrinate		motion sickness		Combination of diphenhydramine with a methylxanthine salt	Dramamine, Gravol
Dicyclomine		IBS			Bentyl
Darifenacin	Selective forM3^[7]	Urinary incontinence^[7]	Few side effects^[7]		Enablex
Flavoxate		Urinary bladder antispasmodic			Urispas
Glycopyrrolate (Glycopyrronium bromide)	NS	Prior to anesthesia to reducesalivary,tracheobronchial, andpharyngeal secretions In combination withneostigmine to prevent muscarinic effects such asbradycardia Sialorrhea Hyperhidrosis COPD	Dry mouth UR Headache Vomiting	Does not cross theblood–brain barrier and has few to no central effects.^[9]	Robinul, Cuvposa, Seebri
Hydroxyzine				Very mild/negligible action	Vistaril, Atarax
Ipratropium bromide	NS	Asthma andbronchitis^[5]	Bronchial vasodilation	Lacksmucociliary excretion inhibition.^[5]	Atrovent and Apovent
Mebeverine		IBS in its primary form (e.g., Abdominal Pain, Bloating, Constipation, and Diarrhea). Irritable bowel syndrome associated with organic lesions of the gastrointestinal tract. (e.g., diverticulosis & diverticulitis, etc.).	skin rashes	A muscolotropic spasmolytic with a strong and selective action on the smooth muscle spasm of the gastrointestinal tract, in particular of the colon.	Colofac, Duspatal, Duspatalin
Oxybutynin	M1/3/4 selective	overactive bladder urge incontinence			Ditropan
Pirenzepine	M1-selective^[5]	inpeptic ulcer (not much anymore)^[5]	(fewer than non-selective ones)^[5]	Inhibitsgastric secretion^[5]
Procyclidine	NS	Drug-induced parkinsonism, akathisia and acute dystonia PD Idiopathic or secondary dystonia	Overdose produces confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations
Scopolamine (L-Hyoscine)	NS	Same uses as atropine^[5] Motion sickness^[5]	as atropine^[5] sedation^[5]	CD [5]	Scopace, Transderm-Scop, Maldemar, Buscopan
Solifenacin		overactive bladder (OAB) Urgency (urge incontinence)		Competitive antagonist	Vesicare
Tropicamide	NS	producemydriasis andcycloplegia in diagnostics^[5]	may causeocular hypertension^[5]	Short acting,CD [5]
Tiotropium		COPD			Spiriva
Trihexyphenidyl/Benzhexol	M1 selective	PD	Drug at relative dose has 83% activity of atropine, thus has the same side-effects		Artane
Tolterodine		urge incontinence			Detrusitol, Detrol

Themuscarinic acetylcholine receptor subtypesectivities of a large number of antimuscarinic drugs have been reviewed.^[10]

Binding affinities

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Anticholinergics

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Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
3-Quinuclidinyl benzilate	0.035–0.044	0.027–0.030	0.080–0.088	0.034–0.037	0.043–0.065	Human	^[11]^[12]
4-DAMP	0.57–0.58	3.80–7.3	0.37–0.52	0.72–1.17	0.55–1.05	Human	^[13]^[14]
AF-DX 250	427	55.0	692	162	3020	Human	^[13]
AF-DX 384	30.9	6.03	66.1	10.0	537	Human	^[13]
AQ-RA 741	28.8	4.27	63.1	6.46	832	Human	^[13]
Atropine	0.21–0.50	0.76–1.5	0.15–1.1	0.13–0.6	0.21–1.7	Human	^[11]^[15]^[14]
Benzatropine (benztropine)	0.231	1.4	1.1	1.1	2.8	Human	^[11]
Biperiden	0.48	6.3	3.9	2.4	6.3	Human	^[11]
Darifenacin	5.5–13	47–77	0.84–2.0	8.6–22	2.3–5.4	Human	^[14]^[16]
Dicycloverine (dicyclomine)	57 (IC₅₀)	415 (IC₅₀)	67 (IC₅₀)	97 (IC₅₀)	53 (IC₅₀)	Human/rat	^[15]
Glycopyrrolate	0.37	1.38	1.31	0.41	1.30	Human	^[9]
Hexahydrodifenidol	11	200	16	76 (IC₅₀)	83	Human/rat	^[15]
Hexahydrosiladifenidol	44	249	10	298 (IC₅₀)	63	Human/rat	^[15]
(R)-Hexbutinol	2.09	20.9	2.14	3.02	5.50	Human	^[13]
Hexocyclium	2.3	23	1.4	5.5	3.7	Human/rat	^[15]
Himbacine	107	10.0	93.3	11.0	490	Human	^[13]
Ipratropium	0.49	1.5	0.51	0.66	1.7	Human	^[16]
Methoctramine	16–50	3.6–14.4	118–277	31.6–38.0	57–313	Human	^[15]^[13]^[17]
N-Methylscopolamine	0.054–0.079	0.083–0.251	0.052–0.099	0.026–0.097	0.106–0.125	Human	^[13]
Orphenadrine	48	213	120	170	129	Human	^[12]
Otenzepad (AF-DX 116)	1300	186	838	1800 (IC₅₀)	2800	Human/rat	^[15]
Oxybutynin	0.66	13	0.72	0.54	7.4	Human	^[14]
pFHHSiD	22.4	132	15.5	31.6	93.3	Human	^[13]
Pirenzepine	6.3–8	224–906	75–180	17–37	66–170	Human	^[11]^[15]^[13]^[14]
Procyclidine	4.6	25	12.4	7	24	Human	^[11]
Propiverine	476	2970	420	536	109	Human	^[14]
Scopolamine (hyoscine)	1.1	2.0	0.44	0.8	2.07	Human	^[11]
Silahexacyclium	2.0	35	1.2	3.2	2.0	Human/rat	^[15]
Timepidium	34	7.7	31	18	11	Human	^[14]
Tiquizium	4.1	4.0	2.8	3.6	8.2	Human	^[14]
Trihexyphenidyl	1.6	7	6.4	2.6	15.9	Human	^[11]
Tripitamine (tripitramine)	1.58	0.27	38.25	6.41	33.87	Human	^[17]
Zamifenacin	55	153	10	68	34	Human	^[14]
Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

Antihistamines

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Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
Brompheniramine	25700	32400	50100	67600	28800	Human	^[18]
Chlorphenamine (chlorpheniramine)	19000	17000	52500	77600	28200	Human	^[18]
Cyproheptadine	12	7	12	8	11.8	Human	^[12]
Diphenhydramine	80–100	120–490	84–229	53–112	30–260	Human	^[11]^[19]
Doxylamine	490	2100	650	380	180	Human	^[19]
Mequitazine	5.6	14	5.3	11.1	11.0	Human	^[12]
Terfenadine	8710	8510	5250	30900	11200	Human	^[18]
Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

Antidepressants

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Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
Amitriptyline	14.7	11.8	12.8	7.2	15.7	Human	^[12]
Bupropion	>35,000	>35,000	>35,000	>35,000	>35,000	Human	^[12]
Citalopram	1430	ND	ND	ND	ND	Human	^[20]
Desipramine	110	540	210	160	143	Human	^[12]
Desmethylcitalopram	>10000	>10000	>10000	>10000	>10000	Human	^[21]
Desmethyldesipramine	404	927	317	629	121	Human	^[21]
Desvenlafaxine	>10000	>10000	>10000	>10000	>10000	Human	^[22]
Dosulepin (dothiepin)	18	109	38	61	92	Human	^[12]
Doxepin	18–38	160–230	25–52	20–82	5.6–75	Human	^[19]^[12]
Escitalopram	1242	ND	ND	ND	ND	Human	^[20]
Etoperidone	>35000	>35000	>35000	>35000	>35000	Human	^[12]
Femoxetine	92	150	220	470	400	Human	^[12]
Fluoxetine	702–1030	2700	1000	2900	2700	Human	^[12]^[20]
Fluvoxamine	31200	ND	ND	ND	ND	Human	^[20]
Imipramine	42	88	60	112	83	Human	^[12]
Lofepramine	67	330	130	340	460	Human	^[12]
Norfluoxetine	1200	4600	760	2600	2200	Human	^[12]
Nortriptyline	40	110	50	84	97	Human	^[12]
Paroxetine	72–300	340	80	320	650	Human	^[12]^[20]
Sertraline	427–1300	2100	1300	1400	1900	Human	^[12]^[20]
Tianeptine	>10000	>10000	>10000	>10000	>10000	Human	^[23]
Trazodone	>35,000	>35,000	>35,000	>35,000	>35,000	Human	^[19]^[12]
Venlafaxine	>35000	>35000	>35000	>35000	>35000	Human	^[12]
Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

Antipsychotics

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Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
Amisulpride	>10,000	>10,000	>10,000	>10,000	>10,000	Human	^[24]
Aripiprazole	6780	3510	4680	1520	2330	Human	^[25]
Asenapine	>10000	>10000	>10000	>10000	ND	Human	^[26]
Bromperidol	7600	1800	7140	1700	4800	Human	^[11]
Chlorprothixene	11	28	22	18	25	Human	^[11]
Chlorpromazine	25	150	67	40	42	Human	^[11]
Clozapine	1.4–31	7–204	6–109	5–27	5–26	Human	^[11]^[26]^[27]^[28]
Cyamemazine (cyamepromazine)	13	42	32	12	35	Human	^[29]
N-Desmethylclozapine	67.6	414.5	95.7	169.9	35.4	Human	^[30]
Fluperlapine	8.8	71	41	14	17	Human	^[11]
Fluphenazine	1095	7163	1441	5321	357	Human	^[31]
Haloperidol	>10000	>10000	>10000	>10000	>10000	Human	^[26]^[27]
Iloperidone	4898	3311	>10000	8318	>10000	Human	^[32]
Loxapine	63.9–175	300–590	122–390	300–2232	91–241	Human	^[11]^[33]
Melperone	>15000	2400	>15000	4400	>15000	Human	^[11]
Mesoridazine	10	15	90	19	60	Human	^[11]
Molindone	ND	ND	>10000	ND	ND	Human	^[34]
Olanzapine	1.9–73	18–96	13–132	10–32	6–48	Human	^[26]^[27]^[28]
Perphenazine	ND	ND	1848	ND	ND	Human	^[34]
Pimozide	ND	ND	1955	ND	ND	Human	^[34]
Quetiapine	120–135	630–705	225–1320	660–2990	2990	Human	^[26]^[27]
Remoxipride	>10000	>10000	>10000	>10000	ND	Human	^[26]
Rilapine	190	470	1400	1000	1100	Human	^[11]
Risperidone	11000	≥3700	13000	≥2900	>15000	Human	^[11]^[26]
Sertindole	ND	ND	2692	ND	ND	Human	^[34]
Tenilapine	260	62	530	430	660	Human	^[11]
Thioridazine	2.7	14	15	9	13	Human	^[11]
Thiothixene	>10000	>10000	>10000	>10000	5376	Human	^[35]
cis-Thiothixene	2600	2100	1600	1540	4310	Human	^[11]
Tiospirone	630	180	1290	480	3900	Human	^[11]
Trifluoperazine	ND	ND	1001	ND	ND	Human	^[34]
Ziprasidone	≥300	>3000	>1300	>1600	>1600	Human	^[27]^[36]
Zotepine	18	140	73	77	260	Human	^[11]
Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

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^Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH (2006). "Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor".J. Pharmacol. Exp. Ther.318 (2):657–65.doi:10.1124/jpet.106.103382.PMID 16675639.S2CID 15063064.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY,Roth BL (2009)."Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo".Psychopharmacology.205 (1):119–28.doi:10.1007/s00213-009-1521-8.PMC 2821721.PMID 19337725.
^Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, Roth BL, Mailman R (2003)."Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology".Neuropsychopharmacology.28 (8):1400–11.doi:10.1038/sj.npp.1300203.PMID 12784105.
^^a ^b ^c ^d ^e ^f ^gBymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT (1996)."Radioreceptor binding profile of the atypical antipsychotic olanzapine".Neuropsychopharmacology.14 (2):87–96.doi:10.1016/0893-133X(94)00129-N.PMID 8822531.
^^a ^b ^c ^d ^eBymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL (2003). "Muscarinic mechanisms of antipsychotic atypicality".Prog. Neuropsychopharmacol. Biol. Psychiatry.27 (7):1125–43.doi:10.1016/j.pnpbp.2003.09.008.PMID 14642972.S2CID 28536368.
^^a ^bBymaster FP, Falcone JF (2000). "Decreased binding affinity of olanzapine and clozapine for human muscarinic receptors in intact clonal cells in physiological medium".Eur. J. Pharmacol.390 (3):245–8.doi:10.1016/s0014-2999(00)00037-6.PMID 10708730.
^Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M (2003). "Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes".Biochem. Pharmacol.65 (3):435–40.doi:10.1016/s0006-2952(02)01515-0.PMID 12527336.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^Kalkman HO, Subramanian N, Hoyer D (2001)."Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders".Neuropsychopharmacology.25 (6):904–14.doi:10.1016/S0893-133X(01)00285-8.PMID 11750183.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^^a ^b ^c ^d ^eKroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003)."H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs".Neuropsychopharmacology.28 (3):519–26.doi:10.1038/sj.npp.1300027.PMID 12629531.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^Roth, BL; Driscol, J."PDSP K_i Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.

External links

[edit]

Effects of Muscarinic Antagonist
Atropine (Muscarinic Receptor Antagonist), Cardiovascular Pharmacology Concepts, Richard E. Klabunde, PhD
Muscarinic+antagonists at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
MeSH list of agents82018727

Pharmacomodulation

Types

♦Enzyme:Inducer
Inhibitor

♦Ion channel:Opener
Blocker

♦Transporter [Reuptake vsEfflux]:Enhancer (RE)
Inhibitor (RI)
Releaser (RA)

♦ Miscellaneous:Precursor
Cofactor

Classes

Enzyme

seeEnzyme inhibition

Ion channel

SeeIon channel modulators

Receptor &
transporter

BA/M

Adrenergic	Adrenergic receptor agonist (α β (1 2)) Adrenergic receptor antagonist (α (1 2) β) Norepinephrine reuptake inhibitor (NRI)
Dopaminergic	Dopamine receptor agonist Dopamine receptor antagonist Dopamine reuptake inhibitor (DRI)
Histaminergic	Histamine receptor agonist Histamine receptor antagonist (H₁ H₂ H₃)
Serotonergic	Serotonin receptor agonist Serotonin receptor antagonist (5-HT₃) Serotonin reuptake inhibitor (SRI)

GABAergic	GABA receptor agonist GABA receptor antagonist GABA reuptake inhibitor (GRI)
Glutamatergic	Glutamate receptor agonist (AMPA) Glutamate receptor antagonist (NMDA) Glutamate reuptake inhibitor

Cholinergic

Cannabinoidergic

Opioidergic

Other

Miscellaneous

Cofactor (seeEnzyme cofactors)
Precursor (seeAmino acids)

Medical uses

Drugs forfunctional gastrointestinal disorders (A03)

Drugs for
functional
bowel
disorders

Antimuscarinics

Tertiary amino group	Camylofin Dicycloverine Difemerine Dihexyverine Mebeverine Oxyphencyclimine Piperidolate Rociverine Trimebutine
Quaternary ammonium compounds	Benzilone Bevonium Diphemanil Fenpiverinium Glycopyrronium Hexocyclium Isopropamide Mepenzolate Methantheline Otilonium Oxyphenonium Penthienate Pipenzolate Poldine Prifinium Propantheline Tiemonium Timepidium Tridihexethyl

Phosphodiesterase
inhibitors

Acting on
serotonin receptors

Other

Belladonna
and derivatives
(antimuscarinics)

Tertiary amines:Atropine
Hyoscyamine

Propulsives

v t e Urologicals, including antispasmodics (G04B)
Acidifiers	Ammonium chloride Calcium chloride
Urinary antispasmodics (primarilyantimuscarinics)	Darifenacin Desfesoterodine Emepronium Fesoterodine Flavoxate Imidafenacin Meladrazine Mirabegron Oxybutynin Propiverine Solifenacin Terodiline Tolterodine Trospium chloride Vibegron
Other urologicals	Urea analogues:Acetohydroxamic acid Salicylhydroxamic acid Other:Collagen Dapoxetine Dimethyl sulfoxide Magnesium hydroxide Pentosan polysulfate Phenazopyridine Phenyl salicylate Succinimide Tiopronin

Antiparkinson agents (N04)

Dopaminergics

DA precursors	Levodopa^# (+benserazide,+carbidopa,+carbidopa/entacapone) Foslevodopa (+foscarbodipa) Melevodopa (+carbidopa)
DA receptor agonists	Ergoline:Bromocriptine Cabergoline Dihydroergocryptine Lisuride Pergolide Non-ergoline:Apomorphine Piribedil Pramipexole Ropinirole Rotigotine Talipexole
MAO-B inhibitors	Rasagiline Safinamide Selegiline
COMT inhibitors	Entacapone Opicapone Tolcapone
AAAD inhibitors	Benserazide (+levodopa) Carbidopa^# (+carbidopa,+melevodopa,+carbidopa/entacapone) Foscarbidopa (+foslevodopa)

Anticholinergics

Others

Adamantanes (e.g.,amantadine,memantine,rimantadine)
Adenosine receptor antagonists (e.g.,caffeine,istradefylline)
Budipine

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Hallucinogens

Psychedelics
(5-HT_2AR agonists)

Tryptamines (e.g.,DMT,psilocin,psilocybin,bufotenin,5-MeO-DMT,AMT)
Phenethylamines (e.g.,mescaline,2C-B,DOM,MDA,TMA,2C-B-FLY,25I-NBOMe)
Lysergamides (e.g.,LSD,ergine,isoergine)
Others (e.g.,quipazine,efavirenz)

For a full list of serotonergic psychedelics, see the navboxhere and the listhere instead.

Dissociatives
(NMDAR antagonists)

Arylcyclo‐ hexylamines	Ketamine-related: 2-Fluorodeschloroketamine Arketamine ((R)-ketamine) Deschloroketamine Ethketamine (N-Ethylnorketamine) Esketamine ((S)-ketamine) Ketamine Methoxetamine Methoxmetamine Methoxyketamine MXiPr Norketamine Tiletamine PCP-related: 2'-Oxo-PCE 3-HO-PCE 3-HO-PCP 3-MeO-PCE 3-MeO-PCMo 3-MeO-PCP 3-MeO-PCPr 3-MeO-PCPy 4-MeO-PCP BDPC Dieticyclidine (PCDE) Eticyclidine (PCE) PCPr Phencyclidine (PCP) Rolicyclidine (PCPy) Tenocyclidine (TCP) Others:BTCP Gacyclidine PRE-084
Adamantanes	Amantadine Memantine Rimantadine
Diarylethylamines	Diphenidine Ephenidine Fluorolintane Methoxphenidine
Morphinans	Dextrallorphan Dextromethorphan Dextrorphan Racemethorphan Racemorphan
Others	2-EMSB 2-MDP 8A-PDHQ Aptiganel Budipine Delucemine Dexoxadrol Dizocilpine Etoxadrol F-17475 Herkinorin Ibogaine Midafotel NEFA Neramexane Nitrous oxide Noribogaine Perzinfotel RB-64 Remacemide Selfotel Xenon

Deliriants
(mAChR antagonists)

Cannabinoids
(CB₁R agonists)

Natural

Synthetic

AM-x	AM-087 AM-251 AM-279 AM-281 AM-356 AM-374 AM-381 AM-404 AM-411 AM-630 AM-661 AM-678 AM-679 AM-694 AM-735 AM-855 AM-881 AM-883 AM-905 AM-906 AM-919 AM-926 AM-938 AM-1116 AM-1172 AM-1220 AM-1221 AM-1235 AM-1241 AM-1248 AM-1710 AM-1714 AM-1902 AM-2201 AM-2212 AM-2213 AM-2232 AM-2233 AM-2389 AM-3102 AM-4030 AM-4054 AM-4056 AM-4113 AM-6545
CPx	CP 47,497 CP 55,244 CP 55,940 (±)-CP 55,940 (+)-CP 55,940 (-)-CP 55,940
HU-x	HU-210 HU-211 HU-239 HU-243 HU-308 HU-320 HU-331 HU-336 HU-345
JWH-x	JWH-007 JWH-015 JWH-018 JWH-019 JWH-030 JWH-047 JWH-048 JWH-051 JWH-057 JWH-073 JWH-081 JWH-098 JWH-116 JWH-120 JWH-122 JWH-133 JWH-139 JWH-147 JWH-148 JWH-149 JWH-149 JWH-161 JWH-164 JWH-166 JWH-167 JWH-171 JWH-175 JWH-176 JWH-181 JWH-182 JWH-184 JWH-185 JWH-192 JWH-193 JWH-194 JWH-195 JWH-196 JWH-197 JWH-198 JWH-199 JWH-200 JWH-203 JWH-205 JWH-210 JWH-210 JWH-213 JWH-220 JWH-229 JWH-234 JWH-249 JWH-250 JWH-251 JWH-253 JWH-258 JWH-300 JWH-302 JWH-307 JWH-336 JWH-350 JWH-359 JWH-387 JWH-398 JWH-424
Misc.	4-HTMPIPO 5F-AB-FUPPYCA 5F-AB-PINACA 5F-ADB 5F-ADB-PINACA 5F-ADBICA 5F-AMB 5F-APINACA 5F-CUMYL-PINACA 5F-NNE1 5F-PB-22 5F-SDB-006 A-796,260 A-836,339 AB-001 AB-005 AB-CHFUPYCA AB-CHMINACA AB-FUBINACA AB-PINACA ADAMANTYL-THPINACA ADB-CHMINACA ADB-FUBINACA ADB-PINACA ADBICA ADSB-FUB-187 AMB-FUBINACA APICA APINACA APP-FUBINACA CB-13 CUMYL-PICA CUMYL-PINACA CUMYL-THPINACA DMHP EAM-2201 FAB-144 FDU-PB-22 FUB-144 FUB-APINACA FUB-JWH-018 FUB-PB-22 FUBIMINA JTE 7-31 JTE-907 Levonantradol MDMB-CHMICA MDMB-CHMINACA MDMB-FUBINACA MEPIRAPIM MAM-2201 MDA-19 MN-18 MN-25 NESS-0327 NESS-040C5 Nabilone Nabitan NM-2201 NNE1 Org 28611 Parahexyl PTI-1 PTI-2 PX-1 PX-2 PX-3 QUCHIC QUPIC RCS-4 RCS-8 SDB-005 SDB-006 STS-135 THC-O-acetate THC-O-phosphate THJ-018 THJ-2201 UR-144 WIN 55,212-2 XLR-11

For a full list of cannabinoids, see the navboxhere and the listhere instead.

Inhalants
(mixed MoATooltip mechanism of action)

Others

Aminochromes (e.g.,adrenochrome,adrenolutin)
Carbogen
CertainGABA_A receptor positive allosteric modulators (nonbenzodiazepines/Z-drugs) (e.g.,eszopiclone,zaleplon,zolpidem,zopiclone)
CI-966
Cryogenine
Glaucine
Hallucinogenic bolete mushrooms (e.g.,Lanmaoa asiatica)
Harmala alkaloids/β-carbolines (e.g.,harmaline,6-methoxyharmalan)
Iboga alkaloids/azepinoindoles (e.g.,ibogaine)
Isoaminile
Noscapine
Nutmeg (e.g.,myristicin,elemicin)
Oneirogens (e.g.,Calea zacatechichi,galantamine,nicotine,Silene capensis)
Prenoxdiazine
Pukateine

v t e Ophthalmologicals:mydriasis andcycloplegia (S01F)
Anticholinergics/antimuscarinics	Atropine Scopolamine Methylscopolamine Cyclopentolate Homatropine Tropicamide (+phenylephrine)
Sympathomimetics	Ephedrine Hydroxyamphetamine (norpholedrine) Ibopamine Phenylephrine (+ketorolac) Pholedrine

Drugs used forglaucoma preparations andmiosis (S01E)

Sympathomimetics

Parasympathomimetics

muscarinic	Aceclidine Pilocarpine
muscarinic/nicotinic	Acetylcholine Carbachol
acetylcholinesterase inhibitors	Demecarium Ecothiopate Stigmine (Fluostigmine Neostigmine Physostigmine) Paraoxon

Carbonic anhydrase inhibitors/
(sulfonamides)

Beta blocking agents

Prostaglandin analogues (F_2α)

Other agents

Acetylcholine receptor modulators

Muscarinic acetylcholine receptor modulators

mAChRsTooltip Muscarinic acetylcholine receptors

Agonists

Antagonists

Precursors
(andprodrugs)

See also: Receptor/signaling modulators; Nicotinic acetylcholine receptor modulators; Acetylcholine metabolism/transport modulators

Nicotinic acetylcholine receptor modulators

nAChRsTooltip Nicotinic acetylcholine receptors

Agonists
(and PAMsTooltip positive allosteric modulators)

Antagonists
(and NAMsTooltip negative allosteric modulators)

Precursors
(andprodrugs)

See also: Receptor/signaling modulators; Muscarinic acetylcholine receptor modulators; Acetylcholine metabolism/transport modulators

v t e Chemical classes ofpsychoactive drugs
Stimulants	Amphetamine-type/dopamine releasing agents:Alkylamines Cycloalkylaminopropanes Arylpiperazines Benzylpiperazines Phenylpiperazines Phenethylamines Aminorexes/phenyloxazolamines Amphetamines/α-methylphenethylamines Cathinones/β-ketoamphetamines β-Hydroxyamphetamines/cathinols Naphthylaminopropanes Phentermines Phenylisobutylamines/α-ethylphenethylamines α-Propylphenethylamines Phenylmorpholines/phenmetrazines Thiopropamines/thienylaminopropanes Cocaine-type/typical dopamine reuptake inhibitors:Phenethylamines Phenidates/benzylpiperidines Phenylethylpyrrolidines Pyrrolidinophenones Phenyltropanes/cocaine analogues Modafinil-type/atypical dopamine reuptake inhibitors:Modafinil analogues Phenylpiracetams Caffeine-type/adenosine receptor antagonists:Xanthines/methylxanthines Nicotine-type/nicotinic acetylcholine receptor agonists:Nicotine analogues
Depressants	GABA_A receptor positive allosteric modulators:Alcohols/ethanol analogues Barbiturates Benzodiazepines Pyrrolobenzodiazepines Thienobenzodiazepines Thienodiazepines Thienotriazolodiazepines Triazolobenzodiazepines Carbamates Ethers Neuroactive steroids Nonbenzodiazepines β-Carbolines Cyclopyrrolones Imidazopyridines Pyrazolopyrimidines Phenols Piperidinediones Quinazolinones GABA_A receptor agonists:Isoxazoles GHB receptor agonists:1,4-Butanediols α₂δ subunit-containing voltage-gated calcium channel blockers:Gabapentinoids Opioids/μ-opioid receptor agonists:Benzimidazoles Nitazenes Fentanyl analogues/phenylpiperidines Mitragyna alkaloids Morphinans/phenanthrenes Opiates/opium alkaloids Utopioids Antihistamines/H₁ receptor antagonists:Benzimidazoles Diarylmethanes Ethylenediamines Tricyclics Dibenzocycloheptenes
Hallucinogens	Serotonergic psychedelics/serotonin 5-HT_2A receptor agonists:Arylpiperazines Phenylpiperazines Quinolinylpiperazines Cyclized phenethylamines 3-Benzazepines Cyclized tryptamines Azepinoindoles Ibogalogs Iboga alkaloids β-Carbolines Harmala alkaloids Ergolines Lysergamides Simplified/partial lysergamides Phenethylamines (methoxyphenethylamines) 2Cs 25-NB/NBOMes 2C-Os 2C-Ts HOT-x TWEETIOs Amphetamines/α-methylphenethylamines 3Cs Dimethoxyamphetamines/DMAs DOx Alephs Ethylenedioxyamphetamines/EDxx Methylenedioxyamphetamines/MDxx Trimethoxyamphetamines/TMAs BOx FLYs/benzofurans Phenylisobutylamines/α-ethylphenethylamines 4Cs Scalines Ψ-PEAs Tryptamines α-Alkyltryptamines α-Alkyl-β-ketotryptamines 4-Hydroxytryptamines 5-Hydroxytryptamines 5-Methoxytryptamines Miscellaneous Dissociatives/NMDA receptor antagonists:Adamantanes Arylcyclohexylamines Diarylethylamines Morphinans κ-Opioid receptor agonists:Benzomorphans Salvinorins GABA_A receptor agonists:Isoxazoles Deliriants/anticholinergics/muscarinic acetylcholine receptor antagonists:Diarylmethanes Tropanes Others:Cyclized tryptamines Azepinoindoles Iboga alkaloids (Phyto)cannabinoids
Entactogens	Serotonin releasing agents:Phenethylamines 2-Aminoindanes 2-Aminotetralins Amphetamines Benzofuranylaminopropanes Benzothiophenylaminopropanes Ethylenedioxyamphetamines/EDxx Indanylaminopropanes Indolylaminopropanes Methylenedioxyamphetamines/MDxx Tetralinylaminopropanes Tryptamines α-Alkyltryptamines Miscellaneous
Psychiatric drugs	Anxiolytics:Azapirones Benzodiazepines Pyrrolobenzodiazepines Thienobenzodiazepines Thienodiazepines Thienotriazolodiazepines Triazolobenzodiazepines Antidepressants:Tricyclic antidepressants Dibenzazepines Dibenzocycloheptenes Dibenzothiepins Dibenzoxazepines Dibenzoxepins Tetracyclic antidepressants Antipsychotics/dopamine D₂ receptor antagonists or partial agonists:Benzamides Benzimidazoles Benzisothiazoles Benzisoxazoles Butyrophenones Diphenylbutylpiperidines Phenylpiperazines Tricyclics Dibenzazepines Dibenzodiazepines Dibenzothiazepines Dibenzothiepins Dibenzoxazepines Phenothiazines Thienobenzodiazepines Mood stabilizers/anticonvulsants:Gabapentinoids Tricyclics Dibenzazepines Valproates
Others	Nootropics:Racetams Phenylpiracetams Miscellaneous:3-Benzazepines Adamantanes Catecholamines Tetrahydroisoquinolines Yohimbans