Clemastine - Wikipedia

Allergy medication Pharmaceutical compound Clemastine

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a682542
Routes ofadministration	Oral
ATC code	D04AA14 (WHO) R06AA04 (WHO)
Legal status
Legal status	In general: Over-the-counter (OTC)
Pharmacokinetic data
Bioavailability	39.2%
Metabolism	Hepatic
Elimination half-life	21.3 hours
Excretion	Renal
Identifiers
IUPAC name (2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
CAS Number	15686-51-8 Y
PubChem CID	26987
IUPHAR/BPS	6063
DrugBank	DB00283 Y
ChemSpider	25129 Y
UNII	95QN29S1ID
KEGG	D03535 Y
ChEBI	CHEBI:3738 Y
ChEMBL	ChEMBL1626 Y
CompTox Dashboard (EPA)	DTXSID2022832
Chemical and physical data
Formula	C21H26ClNO
Molar mass	343.90 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)[C@](OCC[C@@H]2N(C)CCC2)(c3ccccc3)C
InChI InChI=1S/C21H26ClNO/c1-21(17-7-4-3-5-8-17,18-10-12-19(22)13-11-18)24-16-14-20-9-6-15-23(20)2/h3-5,7-8,10-13,20H,6,9,14-16H2,1-2H3/t20-,21-/m1/s1 Y Key:YNNUSGIPVFPVBX-NHCUHLMSSA-N Y
(verify)

Clemastine, also known as meclastin, is a first-generation H1 histamine antagonist (antihistamine) with anticholinergic properties (drying) and sedative side effects.[1] Like all first-generation antihistamines, it is sedating.[2][3]

Patented in 1960, it came into medical use in 1967.[4]

Medical uses

[edit]

Clemastine is used to relieve hay fever and allergy symptoms, including sneezing; runny nose; and red, itchy, tearing eyes. Prescription strength clemastine is also used to relieve the itching and swelling of hives.[5]

Side effects

[edit]

Overdosage symptoms are paradoxical, ranging from CNS depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, hallucinations, ataxia, loss of coordination, muscle twitching, athetosis, hyperthermia, cyanosis, convulsions, tremors, and hyperreflexia. This may be followed by postictal depression and cardiovascular/respiratory arrest. Other common overdose symptoms include dry mouth, fixed dilated pupils, flushing of the face, and pyrexia. In adults, overdose usually leads to CNS depression, ranging from drowsiness to coma.[6]

Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people.[7][8]

Pharmacology

[edit]

Clemastine is an antihistamine with anticholinergic and sedative effects. Antihistamines competitively bind to histamine receptor sites, thus reducing the neurotransmitter's effects.[9] Effects of histamine (which are countered by antihistamines) include:

• Increased capillary permeability
• Increased capillary dilatation
• Edema (i.e., swelling)
• Pruritus (Itch)
• Gastrointestinal/respiratory smooth muscle constriction

Clemastine inhibits both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, the drug can produce paradoxical effects, including CNS stimulation or depression.

Most antihistamines exhibit some type of anticholinergic activity. Antihistamines act by competitively binding to H1-receptor sites, thus blocking the binding of endogenous histamine. Antihistamines do not chemically inactivate or prevent the normal release of histamine.

Clemastine does also act as FIASMA (functional inhibitor of acid sphingomyelinase).[10]

Clemastine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations are attained in 2–4 hours. Antihistamines are thought to be metabolized in the liver, mostly by mono-/didemethylation and glucuronide conjugation. It is an inhibitor of cytochrome P450 CYP2D6 and may interfere with other drugs metabolized by this isozyme.

Mechanism of action

[edit]

Clemastine is a selective histamine H1 antagonist. It binds to the histamine H1 receptor, thus blocking the action of endogenous histamine, which leads to temporary relief of the negative symptoms caused by histamine.[11]

Society and culture

[edit]

Clemastine is an OTC drug, and is available under many names and dosage forms worldwide. Most common brand name is Tavegyl.[12]

Research

[edit]

Clemastine has been studied for its potential to treat several psychiatric and neurological disorders, including possibly promoting remyelination and myelin repair in conditions like multiple sclerosis (MS) and autism spectrum disorder (ASD) .[13][14][15] Early phase II clinical trials showed promise for promoting remyelination in patients with MS, with clemastine improving nerve conduction velocity in the optic nerve.[16][17] However, a clinical trial (TRAP-MS) was halted in early 2024 after researchers found the disability progression was occurring at a significantly faster rate than anticipated in three participants with MS receiving clemastine.[18][19][20] No clinical trials have been conducted regarding ASD.

References

[edit]

1. ^ "Clemastine". DrugBank.com.
2. ^ "Perspectives on Second-Generation OTC Antihistamines". Pharmacy Times. 2012-03-30. Archived from the original on 2012-05-01.
3. ^ Krouse JH (April 2008). "Allergic rhinitis--current pharmacotherapy". Otolaryngologic Clinics of North America. 41 (2): 347–58, vii. doi:10.1016/j.otc.2007.11.014. PMID 18328373.
4. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 978-3-527-60749-5.
5. ^ "Clemastine". MedlinePlus. U.S. National Library of Medicine.
6. ^ "Clemastine Side Effects: Common, Severe, Long Term". Drugs.com. 23 January 2023. Retrieved 13 December 2023.
7. ^ Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA Internal Medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. PMC 4358759. PMID 25621434.
8. ^ Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, et al. (July 2009). "Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study". Archives of Internal Medicine. 169 (14): 1317–1324. doi:10.1001/archinternmed.2009.229. PMC 2933398. PMID 19636034.
9. ^ Farzam K, Sabir S, O'Rourke MC (2024). "Antihistamines". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 30844215. Retrieved 2024-11-11.
10. ^ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, et al. (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLOS ONE. 6 (8) e23852. Bibcode:2011PLoSO...623852K. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.
11. ^ "Clemastine - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose". Drug Index. Pediatric Oncall. Retrieved 2024-05-23.
12. ^ "Clemastine". International listings. drugs.com. Retrieved 10 May 2015.
13. ^ Jiang S, Wang X, Cao T, Kang R, Huang L (2023). "Insights on therapeutic potential of clemastine in neurological disorders". Frontiers in Molecular Neuroscience. 16 1279985. doi:10.3389/fnmol.2023.1279985. PMC 10568021. PMID 37840769.
14. ^ Leigh S (12 June 2023). "Can this Medication Reverse MS? Brain Biomarker Shows It Can". UCSF. Retrieved 17 April 2024.
15. ^ Khelfaoui H, Ibaceta-Gonzalez C, Angulo MC (April 2024). "Functional myelin in cognition and neurodevelopmental disorders". Cellular and Molecular Life Sciences. 81 (1) 181. doi:10.1007/s00018-024-05222-2. PMC 11016012. PMID 38615095.
16. ^ Riboni-Verri G, Chen BS, McMurran CE, Halliwell GJ, Brown JW, Coles AJ, et al. (2024). "Visual outcome measures in clinical trials of remyelinating drugs". BMJ Neurology Open. 6 (1) e000560. doi:10.1136/bmjno-2023-000560. PMC 10882304. PMID 38389586.
17. ^ Moghaddasi M, Nabovvati M, Koushki A, Soltansanjari M, Sardarinia M, Mohebi N, et al. (June 2020). "Randomized control trial of evaluation of Clemastine effects on visual evoked potential, nerve fiber layer and ganglion cell layer complex in patients with optic neuritis". Clinical Neurology and Neurosurgery. 193 105741. doi:10.1016/j.clineuro.2020.105741. PMID 32145678.
18. ^ Ciccone I (2 March 2024). "Clemastine Arm of TRAP-MS Trial Halted Following Increased Disability Accumulation in Progressive Multiple Sclerosis". NeurologyLive. Retrieved 17 April 2024.
19. ^ Dotinga R (14 March 2024). "Clemastine Tied to Worsening Symptoms in Multidrug MS Trial". Medscape. Retrieved 17 April 2024.
20. ^ Maia M (7 March 2024). "ACTRIMS 2024: An antihistamine may speed MS disease progression". Multiple Sclerosis News Today. Retrieved 17 April 2024.

External links

[edit]

• NIH Medline Plus listing on Clemastine
• The pharmacokinetics and bioavailability of clemastine and phenylpropanolamine in single-component and combination formulations

v t e Antipruritics (D04)
Antihistamines for topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Isothipendyl Mepyramine Pheniramine Promethazine Thenalidine Thonzylamine Tolpropamine Tripelennamine
Anesthetics for topical use	Benzocaine Cinchocaine Dibucaine Lidocaine Oxybuprocaine Pramocaine Quinisocaine Tetracaine
Others	Corticosteroids (e.g., hydrocortisone) Counterirritants (e.g., mint oil, menthol, camphor) Difelikefalin Doxepin Nalfurafine

v t e Antihistamines (R06)
Benzimidazoles (*)	Astemizole Azelastine Bilastine Emedastine Mizolastine Talastine
Diarylmethanes	Diarylmethoxyalkylamines: Bromazine (bromodiphenhydramine) Carbinoxamine Chlorphenoxamine Clemastine Diphenhydramine (+naproxen) Diphenylpyraline Doxylamine Ebastine Orphenadrine Diphenylmethanolpiperidines: Fexofenadine Terfenadine Diphenylmethylpiperazines: Buclizine Cetirizine Levocetirizine Chlorcyclizine Cinnarizine Cyclizine Etodroxizine Hydroxyzine Meclizine Oxatomide Phenylpyridinylpropanamines: Brompheniramine Chlorphenamine Dexbrompheniramine (+pseudoephedrine) Dexchlorpheniramine (+betamethasone) Pheniramine Others: Acrivastine Bamipine Dimetindene Phenyltoloxamine Pyrrobutamine Quifenadine Triprolidine
Ethylenediamines	Antazoline Chloropyramine Histapyrrodine Mepyramine (pyrilamine) Methapyrilene Phenbenzamine Thenalidine Tripelennamine (pyribenzamine)
Tricyclics	Dibenzocycloheptenes: Antidepressants (e.g., amitriptyline) Azatadine Cyproheptadine Deptropine Desloratadine Ketotifen Loratadine Rupatadine Phenothiazines: Alimemazine Fenethazine Hydroxyethylpromethazine Isothipendyl Mequitazine Methdilazine Oxomemazine Promethazine Others: Antidepressants (e.g., doxepin, mirtazapine, trimipramine) Epinastine Latrepirdine Mebhydrolin Olopatadine Perlapine Phenindamine Pimethixene
Others	Phenylpiperazines: Antidepressants (e.g., trazodone) Phenbenzamine
For topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Doxepin Isothipendyl Mepyramine (pyrilamine) Promethazine

v t e Hallucinogens
Psychedelics(5-HT2A 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., efavirenz, IHCH-7113, MK-212, quipazine, RH-34) For a full list of serotonergic psychedelics, see the navbox here and the list here instead.
Dissociatives(NMDA antagonists)	Arylcyclohexylamines (e.g., ketamine (K), phencyclidine (PCP), methoxetamine (MXE), tiletamine) Adamantanes (e.g., memantine, amantadine) Diarylethylamines (e.g., diphenidine, ephenidine, methoxphenidine) Morphinans (e.g., dextromethorphan (DXM), dextrorphan (DXO)) Inhalants (e.g., nitrous oxide (N2O), xenon (Xe)) Others (e.g., alkyl nitrites/poppers, aptiganel, dexoxadrol, dizocilpine (MK-801), etoxadrol, selfotel) For a full list of dissociatives, see the navbox here instead.
Deliriants(mACh antagonists)	Tropanes: Atropine Hyoscyamine Scopolamine (hyoscine) Antihistamines: Brompheniramine Chloropyramine Chlorphenamine (chlorpheniramine) Clemastine Cyclizine Cyproheptadine Dimenhydrinate Diphenhydramine Doxylamine Meclizine Mepyramine Pheniramine Phenyltoloxamine Promethazine Tripelennamine Triprolidine Others: Benactyzine Benapryzine (benaprizine) Benzatropine (benztropine) Biperiden BZ (QNB) CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,668 CS-27349 Cycrimine Dicycloverine Ditran (JB-329) EA-3167 EA-3443 EA-3580 EA-3834 Flavoxate JB-318 JB-336 Orphenadrine Oxybutynin Procyclidine Tolterodine Trihexyphenidyl Tropicamide Tropine benzilate WIN-2299
KOR agonists	Salvinoids (terpenoids): 2-EMSB 2-MMSB RB-64 (22-thiocyanatosalvinorin A) Salvinorin A Benzomorphans: Alazocine Bremazocine Cyclazocine Ketazocine Metazocine MR-2034 Pentazocine Phenazocine Morphinans: Butorphanol Cyclorphan Cyprenorphine Diprenorphine Heroin Levallorphan Levomethorphan Levorphanol Morphine Nalbuphine Nalmefene Nalorphine Oxilorphan Proxorphan Racemethorphan Racemorphan Xorphanol Arylacetamides: Enadoline LPK-26 Niravoline Spiradoline U-50488 U-69593 Others: HZ-2 Tifluadom
GABAA agonists	Isoxazoles: Gaboxadol (THIP) Ibotenic acid (Amanita muscaria) Muscimol (Amanita muscaria) Indirect GABAA receptor agonists: GABAA receptor positive allosteric modulators (nonbenzodiazepines/Z-drugs) (e.g., eszopiclone, zaleplon, zolpidem, zopiclone) GABA reuptake inhibitors (e.g., CI-966)
Oneirogens(unknown mech.)	Harmala alkaloids/β-carbolines (e.g., harmine, harmaline, tetrahydroharmine, 6-methoxyharmalan, 6-MeO-THH) (found in Peganum harmala, Banisteriopsis caapi) Iboga alkaloids/azepinoindoles (e.g., ibogaine, noribogaine) (found in Tabernanthe iboga)
Cannabinoids(CB1 agonists)	Phytocannabinoids (e.g., Δ9-THC (dronabinol), CBN, Δ8-THC) Synthetic cannabinoids (e.g., nabilone, JWH-018, JWH-073, HU-210) For a full list of cannabinoids, see the navbox here and the list here instead.
Others	Aminochromes (e.g., adrenochrome, adrenolutin) Carbogen Glaucine Hallucinogenic bolete mushrooms (e.g., Lanmaoa asiatica) Jenkem Kykeon (Eleusinian Mysteries) Nutmeg (e.g., myristicin, elemicin) Soma (haoma)
See also: Psychedelics Dissociatives Entactogens Stimulants Depressants List of hallucinogens

Pharmacodynamics

v t e Histamine receptor modulators H1 Agonists 2-Pyridylethylamine Betahistine Histamine HTMT L-Histidine UR-AK49 Antagonists First-generation (sedating): 4-Methyldiphenhydramine Alimemazine Antazoline Azatadine Bamipine Benzatropine (benztropine) Bepotastine Bromazine Brompheniramine Buclizine Captodiame Carbinoxamine Chlorcyclizine Chloropyramine Chlorothen Chlorphenamine Chlorphenoxamine Cinnarizine Clemastine Clobenzepam Clocinizine Cloperastine Cyclizine Cyproheptadine Dacemazine Decloxizine Deptropine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Dimetindene Diphenhydramine Diphenylpyraline Doxylamine Embramine Etodroxizine Etybenzatropine (ethylbenztropine) Etymemazine Fenethazine Flunarizine Histapyrrodine Homochlorcyclizine Hydroxyethylpromethazine Hydroxyzine Isopromethazine Isothipendyl LY-2624803 (HY-10275) Meclozine Medrylamine Mepyramine (pyrilamine) Mequitazine Methafurylene Methapyrilene Methdilazine Moxastine NBI-75043 Orphenadrine Oxatomide Oxomemazine Perlapine Phenindamine Pheniramine Phenyltoloxamine Pimethixene Piperoxan Pipoxizine Promethazine Propiomazine Pyrrobutamine Talastine Thenalidine Thenyldiamine Thiazinamium Thonzylamine Tolpropamine Tripelennamine Triprolidine Second/third-generation (non-sedating): Acrivastine Alinastine Astemizole Azelastine Bamirastine Barmastine Bepiastine Bepotastine Bilastine Cabastinen Carebastine Cetirizine Clemastine Clemizole Clobenztropine Desloratadine Dorastine Ebastine Efletirizine Emedastine Epinastine Fexofenadine Flezelastine Ketotifen Latrepirdine Levocabastine Levocetirizine Linetastine Loratadine Mapinastine Mebhydrolin Mizolastine Moxastine Noberastine Octastine Olopatadine Perastine Pibaxizine Piclopastine Quifenadine (phencarol) Rocastine Rupatadine Setastine Sequifenadine (bicarphen) Talastine Temelastine Terfenadine Vapitadine Zepastine Others: Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, brilaroxazine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine) Phenylpiperazine antidepressants (e.g., hydroxynefazodone, nefazodone, trazodone, triazoledione) Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline) Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine) Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene) Unknown/unsorted: Azanator Belarizine Elbanizine Flotrenizine GSK1004723 Napactadine Tagorizine Trelnarizine Trenizine H2 Agonists Amthamine Betazole Dimaprit Histamine HTMT Impromidine L-Histidine UR-AK49 Antagonists Bisfentidine Burimamide Cimetidine Dalcotidine Donetidine Ebrotidine Etintidine Famotidine Isolamtidine Lafutidine Lamtidine Lavoltidine (loxtidine) Lupitidine Metiamide Mifentidine Niperotidine Nizatidine Osutidine Oxmetidine Pibutidine Quisultazine (quisultidine) Ramixotidine Ranitidine Roxatidine Sufotidine Tiotidine Tuvatidine Venritidine Xaltidine Zolantidine H3 Agonists α-Methylhistamine BP 2.94 Cipralisant (GT-2331) GT-2203 (VUF-5296) Histamine Imetit Immepip Immethridine (BP-1-5375) L-Histidine Methimepip Proxyfan SCH-50971 VUF-5297 Antagonists A-349821 A-423579 ABT-239 ABT-652 AZD5213 Bavisant Betahistine Burimamide Ciproxifan Clobenpropit Conessine Enerisant GSK-189254 Impentamine Iodophenpropit Irdabisant JNJ-5207852 NNC 38-1049 PF-03654746 Pitolisant SCH-79687 Thioperamide VUF-5681 H4 Agonists 4-Methylhistamine α-Methylhistamine Histamine L-Histidine OUP-16 VUF-8430 Antagonists JNJ-7777120 Mianserin Seliforant Thioperamide Toreforant VUF-6002 See also Receptor/signaling modulators Monoamine metabolism modulators Monoamine reuptake inhibitors v t e Muscarinic acetylcholine receptor modulators mAChRsTooltip Muscarinic acetylcholine receptors Agonists 77-LH-28-1 AC-42 AC-260,584 Aceclidine Acetylcholine AF30 AF150(S) AF267B Alvameline AQRA-741 Arecoline Bethanechol Butyrylcholine Carbachol CDD-0034 CDD-0078 CDD-0097 CDD-0098 CDD-0102 Cevimeline Choline cis-Dioxolane Desmethylclozapine (norclozapine) Ethoxysebacylcholine Guvacoline Itameline LY-593,039 L-689,660 LY-2,033,298 McNA343 Methacholine Milameline Muscarine NGX-267 Ocvimeline Oxotremorine PD-151,832 Pilocarpine RS86 Sabcomeline SDZ 210-086 Sebacylcholine Suberyldicholine Talsaclidine Tazomeline Thiopilocarpine Vedaclidine VU-0029767 VU-0090157 VU-0152099 VU-0152100 VU-0238429 WAY-132,983 Xanomeline YM-796 Antagonists 3-Quinuclidinyl benzilate 4-DAMP Aclidinium bromide (+formoterol) Abediterol AF-DX 250 AF-DX 384 Ambutonium bromide Anisodamine Anisodine Antihistamines (first-generation) (e.g., brompheniramine, buclizine, captodiame, chlorphenamine (chlorpheniramine), cinnarizine, clemastine, cyproheptadine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, meclizine, mequitazine, perlapine, phenindamine, pheniramine, phenyltoloxamine, promethazine, propiomazine, triprolidine) AQ-RA 741 Atropine Atropine methonitrate Atypical antipsychotics (e.g., clozapine, fluperlapine, olanzapine (+fluoxetine), rilapine, quetiapine, tenilapine, zotepine) Benactyzine Benzatropine (benztropine) Benzilone Benzilylcholine mustard Benzydamine Bevonium BIBN 99 Biperiden Bornaprine Camylofin CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 Caramiphen Cimetropium bromide Clidinium bromide Cloperastine CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Desfesoterodine Dexetimide DIBD Dicycloverine (dicyclomine) Dihexyverine Difemerine Diphemanil metilsulfate Ditran Drofenine EA-3167 EA-3443 EA-3580 EA-3834 Emepronium bromide Etanautine Etybenzatropine (ethybenztropine) Fenpiverinium Fentonium bromide Fesoterodine Flavoxate Glycopyrronium bromide (+beclometasone/formoterol, +indacaterol, +neostigmine) Hexahydrodifenidol Hexahydrosiladifenidol Hexbutinol Hexocyclium Himbacine HL-031,120 Homatropine Imidafenacin Ipratropium bromide (+salbutamol) Isopropamide J-104,129 Hyoscyamine Mamba toxin 3 Mamba toxin 7 Mazaticol Mebeverine Meladrazine Mepenzolate Methantheline Methoctramine Methylatropine Methylhomatropine Methylscopolamine Metixene Muscarinic toxin 7 N-Ethyl-3-piperidyl benzilate N-Methyl-3-piperidyl benzilate Nefopam Octatropine methylbromide (anisotropine methylbromide) Orphenadrine Otenzepad (AF-DX 116) Otilonium bromide Oxapium iodide Oxitropium bromide Oxybutynin Oxyphencyclimine Oxyphenonium bromide PBID PD-102,807 PD-0298029 Penthienate Pethidine pFHHSiD Phenglutarimide Phenyltoloxamine Pipenzolate bromide Piperidolate Pirenzepine Piroheptine Pizotifen Poldine Pridinol Prifinium bromide Procyclidine Profenamine (ethopropazine) Propantheline bromide Propiverine Quinidine 3-Quinuclidinyl thiochromane-4-carboxylate Revefenacin Rociverine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine (hyoscine) Scopolamine butylbromide (hyoscine butylbromide) Silahexacyclium Sofpironium bromide Solifenacin SSRIsTooltip Selective serotonin reuptake inhibitors (e.g., femoxetine, paroxetine) Telenzepine Terodiline Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tiemonium iodide Timepidium bromide Tiotropium bromide Tiquizium bromide Tofenacin Tolterodine Tricyclic antidepressants (e.g., amitriptyline (+perphenazine), amitriptylinoxide, butriptyline, cidoxepin, clomipramine, desipramine, desmethyldesipramine, dibenzepin, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nitroxazepine, northiaden (desmethyldosulepin), nortriptyline, protriptyline, quinupramine, trimipramine) Tridihexethyl Trihexyphenidyl Trimebutine Tripitamine (tripitramine) Tropacine Tropatepine Tropicamide Tropine benzilate Trospium chloride Typical antipsychotics (e.g., chlorpromazine, chlorprothixene, cyamemazine (cyamepromazine), loxapine, mesoridazine, thioridazine) Umeclidinium bromide (+vilanterol) WIN-2299 Xanomeline Zamifenacin Precursors(and prodrugs) Acetyl-coA Adafenoxate Choline (lecithin) Citicoline Cyprodenate Dimethylethanolamine Glycerophosphocholine Meclofenoxate (centrophenoxine) Phosphatidylcholine Phosphatidylethanolamine Phosphorylcholine Pirisudanol See also Receptor/signaling modulators Nicotinic acetylcholine receptor modulators Acetylcholine metabolism/transport modulators v t e Sigma receptor modulators σ1 Agonists: 3-PPP 4-PPBP 5-MeO-DMT Alazocine (SKF-10047) Amantadine Arketamine BD-737 BD-1052 Blarcamesine Captodiame Citalopram CGRPTooltip Calcitonin gene-related peptide Cloperastine Cocaine Cutamesine (SA-4503) Cyclazocine Dehydroepiandrosterone (DHEA) (prasterone) Dehydroepiandrosterone sulfate (DHEA-S) (prasterone sulfate) Dextrallorphan Dextromethorphan (DXM) Dextrorphan (DXO) Dimemorfan Dimethyltryptamine (DMT) Ditolylguanidine (DTG) Donepezil Eliprodil Escitalopram Fabomotizole (afobazole) Fluoxetine Fluvoxamine Ifenprodil Igmesine (JO-1784) IPAB Ketamine L-687384 MDMA (midomafetamine) Memantine Methamphetamine Methoxetamine Methylphenidate Nepinalone Neuropeptide Y Noscapine OPC-14523 Opipramol Pentazocine Pentoxyverine (carbetapentane) PRE-084 Pregnenolone Pregnenolone sulfate Pridopidine Racemethorphan (methorphan) Racemorphan (morphanol) UMB-23 UMB-82 Antagonists: 3-PPP AC-927 BD-1008 BD-1031 BD-1047 BD-1060 BD-1063 BD-1067 BMY-14802 (BMS-181100) CM-156 Dup-734 E-5842 E-52862 (S1RA) Haloperidol LR-132 LR-172 MS-377 NE-100 NPC-16377 Panamesine (EMD-57455) PD-144418 Pentazocine Progesterone Rimcazole (BW-234U) Sertraline SR-31742A Allosteric modulators: Phenytoin; Positive: Methylphenylpiracetam SOMCL-668 Unknown/unsorted: 3-Methoxydextrallorphan 3-MeO-PCP 4C-T-2 4-IBP 4-IPBS 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Amitriptyline Azidopamil Chlorpromazine Clemastine Clomipramine Clorgiline D-Deprenyl DiPTTooltip N,N-Diisopropyltryptamine DPTTooltip N,N-Dipropyltryptamine Ibogaine Imipramine KCR-12-83.1 Nemonapride Noribogaine RHL-033 RS-67,333 RTI-55 Saffron Safinamide Selegiline Spipethiane Trifluoperazine W-18 YKP10A σ2 Agonists: 3-PPP Arketamine BD-1047 BD1063 Ditolylguanidine (DTG) DKR-1005 DKR-1051 Haloperidol Ifenprodil Ketamine MDMA (midomafetamine) Methamphetamine OPC-14523 Opipramol PB-28 Phencyclidine Siramesine (Lu 28-179) UKH-1114 Antagonists: AC-927 BD-1008 BD-1067 CM-156 LR-172 MIN-101 Panamesine (EMD-57455) SAS-0132 Zervimesine (CT-1812) Unknown/unsorted: 3-Methoxydextrallorphan 3-MeO-PCE 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Clemastine DiPTTooltip N,N-Diisopropyltryptamine DPTTooltip N,N-Dipropyltryptamine Ibogaine Lu 29-252 Nemonapride Nepinalone Noribogaine Pentazocine RS-67,333 Safinamide TMATooltip 3,4,5-Trimethoxyamphetamine UMB-23 UMB-82 W-18 Unsorted Agonists: Berberine Ethylketazocine Fourphit Metaphit Naluzotan Tapentadol Tenocyclidine Antagonists: AHD1 AZ66 Lamotrigine Naloxone SM-21 UMB-100 UMB-101 UMB-103 UMB-116 YZ-011 YZ-069 YZ-185 Allosteric modulators: SKF-83959 Unknown/unsorted: 18-Methoxycoronaridine BMY-13980 Butaclamol Caramiphen Carvotroline Chlorphenamine (chlorpheniramine) Chlorpromazine Cinnarizine Cinuperone Clocapramine Dezocine EMD-59983 Hypericin (St. John's wort) Fluphenazine Gevotroline (WY-47384) Mepyramine (pyrilamine) Molindone Perphenazine Pimozide Proadifen Promethazine Propranolol Quinidine Remoxipride SL 82.0715 SR-31747A Tiospirone (BMY-13859) Venlafaxine See also: Receptor/signaling modulators