Muscarinic antagonist#Effects

{{short description|Drug that binds to but does not activate muscarinic cholinergic receptors}}{{Multiple issues|Needs more citations. Includes a large table which needs to be turned into prose or removed.|collapsed=yes}}{{Infobox drug class

| Name = Muscarinic acetylcholine receptor antagonist

| Image = L-Scopolamin.svg

| ImageClass = skin-invert-image

| Alt = Scopolamine

| 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 with bradycardia,{{Cite web|url=https://www.medpagetoday.com/cardiology/arrhythmias/72859|title=Hyoscyamine Subs for Pacemaker in Afib with Bradycardia|date=May 14, 2018|website=www.medpagetoday.com}} motion sickness, Parkinson's disease, etc.

| Caption = Skeletal formula of scopolamine, a nonselective antagonist of the muscarinic receptors

| Biological_target = Muscarinic acetylcholine receptors

| ATC_prefix = V

| MeshID = D018727

}}

A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic 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 the parasympathetic 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 the central and peripheral nervous systems.

Drugs with muscarinic antagonist activity are widely used in medicine, in the treatment of low heart rate, overactive bladder, respiratory problems such as asthma and chronic obstructive pulmonary disease (COPD), and neurological problems such as Parkinson's disease and Alzheimer's disease. A number of other drugs, such as antipsychotics and the tricyclic family of antidepressants, have incidental muscarinic antagonist activity which can cause unwanted side effects such as difficulty urinating, dry mouth and skin, and constipation.

Acetylcholine (often abbreviated ACh) is a neurotransmitter whose receptors are proteins found in synapses 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 to muscarine
nicotinic, which respond to nicotine

Most muscarinic receptor antagonists are synthetic chemicals; however, the two most commonly used anticholinergics, scopolamine and atropine, are belladonna alkaloids, and are naturally extracted from plants such as Atropa belladonna, commonly known as {{em|deadly 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 the pupils.{{Cite web|title=Belladonna: MedlinePlus Supplements|url=https://medlineplus.gov/druginfo/natural/531.html|access-date=2020-08-13|website=medlineplus.gov|language=en}}

Muscarinic antagonist effects and muscarinic agonist effects counterbalance each other for homeostasis.

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.{{Cite book|last=Ritter|first=James|url=https://www.worldcat.org/oclc/1081403059|title=Rang and Dale's pharmacology|date=2020|others=R. J. Flower, Graeme Henderson, Yoon Kong Loke, David J. MacEwan, H. P. Rang|isbn=978-0-7020-8060-9|edition=9th|location=Edinburgh|pages=377|oclc=1081403059}}

Effects

Scopolamine and atropine have similar effects on the peripheral nervous system. However, scopolamine has greater effects on the central nervous system (CNS) than atropine due to its ability to cross the blood–brain barrier.{{Cite journal |doi = 10.1177/1756283X16670076|pmid = 28286563|pmc = 5330606|title = Antispasmodic drugs in colonoscopy: A review of their pharmacology, safety and efficacy in improving polyp detection and related outcomes|journal = Therapeutic Advances in Gastroenterology|volume = 10|issue = 1|pages = 101–113|year = 2017|last1 = Sanagapalli|first1 = Santosh|last2 = Agnihotri|first2 = Kriti|last3 = Leong|first3 = Rupert|last4 = Corte|first4 = Crispin John}} At higher-than-therapeutic doses, atropine and scopolamine cause CNS depression characterized by amnesia, fatigue, and reduction in rapid eye movement sleep. Scopolamine (Hyoscine) has anti-emetic activity and is, therefore, used to treat motion sickness.

Antimuscarinics are also used as anti-parkinsonian drugs. In parkinsonism, there is imbalance between levels of acetylcholine and dopamine in the brain, involving both increased levels of acetylcholine and degeneration of dopaminergic 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 the M2 receptors of the heart and antagonizes the activity of acetylcholine. It causes tachycardia by blocking vagal effects on the sinoatrial 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 initial bradycardia. This is because when administered intramuscularly or subcutaneously atropine acts on presynaptic M1 receptors (autoreceptors). Uptake of acetylcholine in axoplasm is prevented and the presynaptic nerve releases more acetylcholine into the synapse, which initially causes bradycardia.

In the atrioventricular node, the resting potential is lowered, which facilitates conduction. This is seen as a shortened PR-interval on an electrocardiogram. It{{clarify|date=June 2015}} has an opposite effect on blood pressure. Tachycardia and stimulation of the vasomotor center causes an increase in blood pressure. But, due to feedback regulation of the vasomotor center, there is a fall in blood pressure due to vasodilation.

Important{{cite book |author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |isbn=0-443-07145-4 }} Page 147 muscarinic antagonists include atropine, hyoscyamine, hyoscine butylbromide and hydrobromide, ipratropium, tropicamide, cyclopentolate, pirenzepine and scopolamine.

Muscarinic antagonists such as ipratropium bromide can also be effective in treating asthma, since acetylcholine is known to cause smooth muscle contraction, especially in the bronchi.

Comparison table

=Overview=

class="wikitable" style="font-size:small;"

!Substance

!Selectivity

!Clinical use

!Adverse effects

!Notes

!Trade names

Atropine (D/L-Hyoscyamine)

|{{abbr|NS|Non-selective antagonism}}

During anesthesia{{cite journal | last=Mirakhur | first=RK | title=Preanaesthetic medication: a survey of current usage | journal=Journal of the Royal Society of Medicine | volume=84 | issue=8 | pages=481–483 |date=August 1991 | pmid=1886116 | pmc=1293378 | doi=10.1177/014107689108400811 }}
Antidote to anticholinesterase poisoning
Atrial fibrillation with bradycardia
Antispasmodic in gastrointestinal hypermotility

|{{abbr|CD|Central nervous system depression}}

|Symax, HyoMax, Anaspaz, Egazil, Buwecon, Cystospaz, Levsin, Levbid, Levsinex, Donnamar, NuLev, Spacol T/S and Neoquess

Atropine methonitrate

|{{abbr|NS|Non-selective antagonism}}

antispasmodic in gastrointestinal hypermotility

| Blocks transmission in ganglia. Lacks CNS effectsTable 10-5 in: {{cite book|title=Rang & Dale's pharmacology|author1=Rod Flower|author2=Humphrey P. Rang|author3=Maureen M. Dale|author4=Ritter, James M.|publisher=Churchill Livingstone|year=2007|isbn=978-0-443-06911-6|location=Edinburgh}}

Aclidinium bromide

|Selective{{Clarify|reason=What receptor is aclidinium selective for?|date=June 2019}}

Bronchospasm
COPD

| Long acting antagonist

| Tudorza

Benztropine

|M1-selective

Parkinson's disease
extrapyramidal symptoms caused by typical and atypical antipsychotics

|Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.

| Cogentin

Cyclopentolate

|{{abbr|NS|Non-selective antagonism}}

produce mydriasis and cycloplegia in diagnostics

may cause ocular hypertension

| Short acting, {{abbr|CD|Central nervous system depression}}

Diphenhydramine

|{{abbr|NS|Non-selective antagonism}}

for extrapyramidal symptoms from typical and atypical antipsychotic medications
antihistamine
sleep aid
Parkinson's disease
management of asthma symptoms

sedation
dry mouth
constipation
urinary retention

| Acts in the central nervous system, blood vessels and smooth muscle tissues

| Benadryl, Nytol

Doxylamine

|{{abbr|NS|Non-selective antagonism}}

antihistamine{{cite web|url=http://www.drugbank.ca/drugs/DB00366|title=Doxylamine|website=www.drugbank.ca|access-date=21 March 2018}}
antiemetic
sleep aid

dizziness
dry mouth

| Unisom

Dimenhydrinate

motion sickness

| Combination of diphenhydramine with a methylxanthine salt

| Dramamine, Gravol

Dicyclomine

| Bentyl

Darifenacin

|Selective for M3

|Urinary incontinence

|Few side effects

|Enablex

Flavoxate

Urinary bladder antispasmodic

| Urispas

Glycopyrrolate (Glycopyrronium bromide)

|{{abbr|NS|Non-selective antagonism}}

Prior to anesthesia to reduce salivary, tracheobronchial, and pharyngeal secretions
In combination with neostigmine to prevent muscarinic effects such as bradycardia
Sialorrhea
Hyperhidrosis
COPD

| Does not cross the blood–brain barrier and has few to no central effects.{{cite journal |last1=Chabicovsky |first1=Monika |last2=Winkler |first2=Swantje |last3=Soeberdt |first3=Michael |last4=Kilic |first4=Ana |last5=Masur |first5=Clarissa |last6=Abels |first6=Christoph |title=Pharmacology, toxicology and clinical safety of glycopyrrolate |journal=Toxicology and Applied Pharmacology |date=1 May 2019 |volume=370 |pages=154–169 |doi=10.1016/j.taap.2019.03.016 |pmid=30905688 |s2cid=85498396 |url=https://pubmed.ncbi.nlm.nih.gov/30905688/ |issn=1096-0333}}

| Robinul, Cuvposa, Seebri

Hydroxyzine

|Very mild/negligible action

| Vistaril, Atarax

Ipratropium bromide

|{{abbr|NS|Non-selective antagonism}}

|Asthma and bronchitis

Bronchial vasodilation

| Lacks mucociliary excretion inhibition.

| 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

| Ditropan

Pirenzepine

|M1-selective

in peptic ulcer (not much anymore)

| (fewer than non-selective ones)

| Inhibits gastric secretion

Procyclidine

|{{abbr|NS|Non-selective antagonism}}

Drug-induced parkinsonism, akathisia and acute dystonia
Parkinson's disease
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)

|{{abbr|NS|Non-selective antagonism}}

Same uses as atropine
Motion sickness

as atropine
sedation

|{{abbr|CD|Central nervous system depression}}

| Scopace, Transderm-Scop, Maldemar, Buscopan

Solifenacin

overactive bladder (OAB)
Urgency (urge incontinence)

| Competitive antagonist

| Vesicare

Tropicamide

|{{abbr|NS|Non-selective antagonism}}

produce mydriasis and cycloplegia in diagnostics

may cause ocular hypertension

| Short acting, {{abbr|CD|Central nervous system depression}}

Tiotropium

COPD

| Spiriva

Trihexyphenidyl/Benzhexol

|M1 selective

|Parkinson's disease

|Drug at relative dose has 83% activity of atropine, thus has the same side-effects

|Artane

Tolterodine

urge incontinence

| Detrusitol, Detrol

The muscarinic acetylcholine receptor subtype sectivities of a large number of antimuscarinic drugs have been reviewed.{{cite journal | vauthors = Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM | title = A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity | journal = Pharmaceutics | volume = 15 | issue = 1 | date = January 2023 | page = 230 | pmid = 36678858 | pmc = 9863833 | doi = 10.3390/pharmaceutics15010230 | doi-access = free | url = }}

=Binding affinities=

==Anticholinergics==

Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
class="wikitable" style="font-size:small;"
3-Quinuclidinyl benzilate	0.035–0.044	0.027–0.030	0.080–0.088	0.034–0.037	0.043–0.065	Human	{{cite journal \| vauthors = Bolden C, Cusack B, Richelson E \| title = Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells \| journal = J. Pharmacol. Exp. Ther. \| volume = 260 \| issue = 2 \| pages = 576–80 \| year = 1992 \| pmid = 1346637 }}
4-DAMP	0.57–0.58	3.80–7.3	0.37–0.52	0.72–1.17	0.55–1.05	Human
AF-DX 250	427	55.0	692	162	3020	Human
AF-DX 384	30.9	6.03	66.1	10.0	537	Human
AQ-RA 741	28.8	4.27	63.1	6.46	832	Human
Atropine	0.21–0.50	0.76–1.5	0.15–1.1	0.13–0.6	0.21–1.7	Human	{{cite journal \| vauthors = Buckley NJ, Bonner TI, Buckley CM, Brann MR \| title = Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells \| journal = Mol. Pharmacol. \| volume = 35 \| issue = 4 \| pages = 469–76 \| year = 1989 \| pmid = 2704370 }}{{cite journal \| vauthors = Moriya H, Takagi Y, Nakanishi T, Hayashi M, Tani T, Hirotsu I \| title = Affinity profiles of various muscarinic antagonists for cloned human muscarinic acetylcholine receptor (mAChR) subtypes and mAChRs in rat heart and submandibular gland \| journal = Life Sci. \| volume = 64 \| issue = 25 \| pages = 2351–8 \| year = 1999 \| pmid = 10374898 \| doi = 10.1016/s0024-3205(99)00188-5}}
Benzatropine (benztropine)	0.231	1.4	1.1	1.1	2.8	Human
Biperiden	0.48	6.3	3.9	2.4	6.3	Human
Darifenacin	5.5–13	47–77	0.84–2.0	8.6–22	2.3–5.4	Human
Dicycloverine (dicyclomine)	57 (IC₅₀)	415 (IC₅₀)	67 (IC₅₀)	97 (IC₅₀)	53 (IC₅₀)	Human/rat
Glycopyrrolate	0.37	1.38	1.31	0.41	1.30	Human
Hexahydrodifenidol	11	200	16	76 (IC₅₀)	83	Human/rat
Hexahydrosiladifenidol	44	249	10	298 (IC₅₀)	63	Human/rat
(R)-Hexbutinol	2.09	20.9	2.14	3.02	5.50	Human
Hexocyclium	2.3	23	1.4	5.5	3.7	Human/rat
Himbacine	107	10.0	93.3	11.0	490	Human
Ipratropium	0.49	1.5	0.51	0.66	1.7	Human	{{cite journal \| vauthors = Hirose H, Aoki I, Kimura T, Fujikawa T, Numazawa T, Sasaki K, Sato A, Hasegawa T, Nishikibe M, Mitsuya M, Ohtake N, Mase T, Noguchi K \| title = Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity \| journal = J. Pharmacol. Exp. Ther. \| volume = 297 \| issue = 2 \| pages = 790–7 \| year = 2001 \| pmid = 11303071 }}
Methoctramine	16–50	3.6–14.4	118–277	31.6–38.0	57–313	Human
N-Methylscopolamine	0.054–0.079	0.083–0.251	0.052–0.099	0.026–0.097	0.106–0.125	Human	{{cite journal \| vauthors = Dörje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR \| title = Antagonist binding profiles of five cloned human muscarinic receptor subtypes \| journal = J. Pharmacol. Exp. Ther. \| volume = 256 \| issue = 2 \| pages = 727–33 \| year = 1991 \| pmid = 1994002 }}
Orphenadrine	48	213	120	170	129	Human
Otenzepad (AF-DX 116)	1300	186	838	1800 (IC₅₀)	2800	Human/rat
Oxybutynin	0.66	13	0.72	0.54	7.4	Human
pFHHSiD	22.4	132	15.5	31.6	93.3	Human
Pirenzepine	6.3–8	224–906	75–180	17–37	66–170	Human
Procyclidine	4.6	25	12.4	7	24	Human
Propiverine	476	2970	420	536	109	Human
Scopolamine (hyoscine)	1.1	2.0	0.44	0.8	2.07	Human
Silahexacyclium	2.0	35	1.2	3.2	2.0	Human/rat
Timepidium	34	7.7	31	18	11	Human
Tiquizium	4.1	4.0	2.8	3.6	8.2	Human
Trihexyphenidyl	1.6	7	6.4	2.6	15.9	Human
Tripitamine (tripitramine)	1.58	0.27	38.25	6.41	33.87	Human	{{cite journal \| vauthors = Maggio R, Barbier P, Bolognesi ML, Minarini A, Tedeschi D, Melchiorre C \| title = Binding profile of the selective muscarinic receptor antagonist tripitramine \| journal = Eur. J. Pharmacol. \| volume = 268 \| issue = 3 \| pages = 459–62 \| year = 1994 \| pmid = 7805774 \| doi = 10.1016/0922-4106(94)90075-2}}
Zamifenacin	55	153	10	68	34	Human
class="sortbottom" \| colspan="8" \| Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

==Antihistamines==

Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
class="wikitable" style="font-size:small;"
Brompheniramine	25700	32400	50100	67600	28800	Human	{{cite journal \| vauthors = Yasuda SU, Yasuda RP \| title = Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes \| journal = Pharmacotherapy \| volume = 19 \| issue = 4 \| pages = 447–51 \| year = 1999 \| pmid = 10212017 \| doi = 10.1592/phco.19.6.447.31041\| s2cid = 39502992 }}
Chlorphenamine (chlorpheniramine)	19000	17000	52500	77600	28200	Human
Cyproheptadine	12	7	12	8	11.8	Human
Diphenhydramine	80–100	120–490	84–229	53–112	30–260	Human	{{cite journal \| vauthors = Krystal AD, Richelson E, Roth T \| title = Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications \| journal = Sleep Med Rev \| volume = 17 \| issue = 4 \| pages = 263–72 \| year = 2013 \| pmid = 23357028 \| doi = 10.1016/j.smrv.2012.08.001 }}
Doxylamine	490	2100	650	380	180	Human
Mequitazine	5.6	14	5.3	11.1	11.0	Human
Terfenadine	8710	8510	5250	30900	11200	Human
class="sortbottom" \| colspan="8" \| Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

==Antidepressants==

Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
class="wikitable" style="font-size:small;"
Amitriptyline	14.7	11.8	12.8	7.2	15.7	Human	{{cite journal \| vauthors = Stanton T, Bolden-Watson C, Cusack B, Richelson E \| title = Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics \| journal = Biochem. Pharmacol. \| volume = 45 \| issue = 11 \| pages = 2352–4 \| year = 1993 \| pmid = 8100134 \| doi = 10.1016/0006-2952(93)90211-e}}
Bupropion	>35,000	>35,000	>35,000	>35,000	>35,000	Human
Citalopram	1430	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human	{{cite journal \| vauthors = Owens JM, Knight DL, Nemeroff CB \| title = [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] \| language = fr \| journal = Encephale \| volume = 28 \| issue = 4 \| pages = 350–5 \| year = 2002 \| pmid = 12232544 }}
Desipramine	110	540	210	160	143	Human
Desmethylcitalopram	>10000	>10000	>10000	>10000	>10000	Human
Desmethyldesipramine	404	927	317	629	121	Human	{{cite journal \| vauthors = Deupree JD, Montgomery MD, Bylund DB \| title = Pharmacological properties of the active metabolites of the antidepressants desipramine and citalopram \| journal = Eur. J. Pharmacol. \| volume = 576 \| issue = 1–3 \| pages = 55–60 \| year = 2007 \| pmid = 17850785 \| pmc = 2231336 \| doi = 10.1016/j.ejphar.2007.08.017 }}
Desvenlafaxine	>10000	>10000	>10000	>10000	>10000	Human	{{cite journal \| vauthors = Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH \| title = Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor \| journal = J. Pharmacol. Exp. Ther. \| volume = 318 \| issue = 2 \| pages = 657–65 \| year = 2006 \| pmid = 16675639 \| doi = 10.1124/jpet.106.103382 \| s2cid = 15063064 }}
Dosulepin (dothiepin)	18	109	38	61	92	Human
Doxepin	18–38	160–230	25–52	20–82	5.6–75	Human
Escitalopram	1242	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Etoperidone	>35000	>35000	>35000	>35000	>35000	Human
Femoxetine	92	150	220	470	400	Human
Fluoxetine	702–1030	2700	1000	2900	2700	Human
Fluvoxamine	31200	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Imipramine	42	88	60	112	83	Human
Lofepramine	67	330	130	340	460	Human
Norfluoxetine	1200	4600	760	2600	2200	Human
Nortriptyline	40	110	50	84	97	Human
Paroxetine	72–300	340	80	320	650	Human
Sertraline	427–1300	2100	1300	1400	1900	Human
Tianeptine	>10000	>10000	>10000	>10000	>10000	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=tianeptine&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
Trazodone	>35,000	>35,000	>35,000	>35,000	>35,000	Human
Venlafaxine	>35000	>35000	>35000	>35000	>35000	Human
class="sortbottom" \| colspan="8" \| Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

==Antipsychotics==

Compound	M₁	M₂	M₃	M₄	M₅	Species	Ref
class="wikitable" style="font-size:small;"
Amisulpride	>10,000	>10,000	>10,000	>10,000	>10,000	Human	{{cite journal \| vauthors = Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL \|author6-link=Bryan Roth \| title = Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo \| journal = Psychopharmacology \| volume = 205 \| issue = 1 \| pages = 119–28 \| year = 2009 \| pmid = 19337725 \| pmc = 2821721 \| doi = 10.1007/s00213-009-1521-8 }}
Aripiprazole	6780	3510	4680	1520	2330	Human	{{cite journal \| vauthors = Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, Roth BL, Mailman R \| title = Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology \| journal = Neuropsychopharmacology \| volume = 28 \| issue = 8 \| pages = 1400–11 \| year = 2003 \| pmid = 12784105 \| doi = 10.1038/sj.npp.1300203 \| doi-access = free }}
Asenapine	>10000	>10000	>10000	>10000	{{abbr\|ND\|No data}}	Human
Bromperidol	7600	1800	7140	1700	4800	Human
Chlorprothixene	11	28	22	18	25	Human
Chlorpromazine	25	150	67	40	42	Human
Clozapine	1.4–31	7–204	6–109	5–27	5–26	Human	{{cite journal \| vauthors = Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL \| title = Muscarinic mechanisms of antipsychotic atypicality \| journal = Prog. Neuropsychopharmacol. Biol. Psychiatry \| volume = 27 \| issue = 7 \| pages = 1125–43 \| year = 2003 \| pmid = 14642972 \| doi = 10.1016/j.pnpbp.2003.09.008 \| s2cid = 28536368 }}{{cite journal \| vauthors = Bymaster FP, Falcone JF \| title = Decreased binding affinity of olanzapine and clozapine for human muscarinic receptors in intact clonal cells in physiological medium \| journal = Eur. J. Pharmacol. \| volume = 390 \| issue = 3 \| pages = 245–8 \| year = 2000 \| pmid = 10708730 \| doi = 10.1016/s0014-2999(00)00037-6}}
Cyamemazine (cyamepromazine)	13	42	32	12	35	Human	{{cite journal \| vauthors = Hameg A, Bayle F, Nuss P, Dupuis P, Garay RP, Dib M \| title = Affinity of cyamemazine, an anxiolytic antipsychotic drug, for human recombinant dopamine vs. serotonin receptor subtypes \| journal = Biochem. Pharmacol. \| volume = 65 \| issue = 3 \| pages = 435–40 \| year = 2003 \| pmid = 12527336 \| doi = 10.1016/s0006-2952(02)01515-0}}
N-Desmethylclozapine	67.6	414.5	95.7	169.9	35.4	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=1973&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
Fluperlapine	8.8	71	41	14	17	Human
Fluphenazine	1095	7163	1441	5321	357	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=fluphenazine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
Haloperidol	>10000	>10000	>10000	>10000	>10000	Human
Iloperidone	4898	3311	>10000	8318	>10000	Human	{{cite journal \| vauthors = Kalkman HO, Subramanian N, Hoyer D \| title = Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders \| journal = Neuropsychopharmacology \| volume = 25 \| issue = 6 \| pages = 904–14 \| year = 2001 \| pmid = 11750183 \| doi = 10.1016/S0893-133X(01)00285-8 \| doi-access = free }}
Loxapine	63.9–175	300–590	122–390	300–2232	91–241	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=loxapine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
Melperone	>15000	2400	>15000	4400	>15000	Human
Mesoridazine	10	15	90	19	60	Human
Molindone	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	>10000	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human	{{cite journal \| vauthors = Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL \| title = H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs \| journal = Neuropsychopharmacology \| volume = 28 \| issue = 3 \| pages = 519–26 \| year = 2003 \| pmid = 12629531 \| doi = 10.1038/sj.npp.1300027 \| doi-access = free }}
Olanzapine	1.9–73	18–96	13–132	10–32	6–48	Human	{{cite journal \| vauthors = Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT \| title = Radioreceptor binding profile of the atypical antipsychotic olanzapine \| journal = Neuropsychopharmacology \| volume = 14 \| issue = 2 \| pages = 87–96 \| year = 1996 \| pmid = 8822531 \| doi = 10.1016/0893-133X(94)00129-N \| doi-access = free }}
Perphenazine	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	1848	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Pimozide	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	1955	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Quetiapine	120–135	630–705	225–1320	660–2990	2990	Human
Remoxipride	>10000	>10000	>10000	>10000	{{abbr\|ND\|No data}}	Human
Rilapine	190	470	1400	1000	1100	Human
Risperidone	11000	≥3700	13000	≥2900	>15000	Human
Sertindole	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	2692	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Tenilapine	260	62	530	430	660	Human
Thioridazine	2.7	14	15	9	13	Human
Thiothixene	>10000	>10000	>10000	>10000	5376	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=thiothixene&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
cis-Thiothixene	2600	2100	1600	1540	4310	Human
Tiospirone	630	180	1290	480	3900	Human
Trifluoperazine	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	1001	{{abbr\|ND\|No data}}	{{abbr\|ND\|No data}}	Human
Ziprasidone	≥300	>3000	>1300	>1600	>1600	Human	{{cite web \| title = PDSP K_i Database \| work = Psychoactive Drug Screening Program (PDSP) \| author1 = Roth, BL \| author2 = Driscol, J \| publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health \| access-date = 14 August 2017 \| url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=ziprasidone&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}
Zotepine	18	140	73	77	260	Human
class="sortbottom" \| colspan="8" \| Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

References

External links

[http://www.pharmatutor.org/pharmacology/ans-pharmacology/anti-cholinergics.html Effects of Muscarinic Antagonist]
[http://cvpharmacology.com/antiarrhy/atropine.htm Atropine (Muscarinic Receptor Antagonist)], Cardiovascular Pharmacology Concepts, Richard E. Klabunde, PhD
{{MeshName|Muscarinic+antagonists}}
{{MeshPharmaList|82018727}}

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Muscarinic antagonist#Effects

Effects

Comparison table

=Overview=

=Binding affinities=

==Anticholinergics==

==Antihistamines==

==Antidepressants==

==Antipsychotics==

See also

References

External links