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Revision as of 22:38, 10 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit		Latest revision as of 19:34, 10 December 2024 edit undoMarbletan (talk | contribs)Extended confirmed users5,460 edits →Pharmacology: not unreferenced
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			{{short description|Allergy medication}}
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	{{Drugbox		{{Drugbox
			| Watchedfields = changed
	| verifiedrevid = 443529714		| verifiedrevid = 460041264
	| IUPAC_name = (2''R'')-2-{2-ethyl}-1-methylpyrrolidine		| IUPAC_name = (2''R'')-2-{2-ethyl}-1-methylpyrrolidine
	| image = Clemastine.svg		| image = Clemastine.svg
			| width = 222
			| image2 = Clemastine ball-and-stick.png
	<!--Clinical data-->		<!--Clinical data-->
	| tradename = Tavist-1		| tradename =
	| Drugs.com = {{drugs.com|monograph|clemastine-fumarate}}		| Drugs.com = {{drugs.com|monograph|clemastine-fumarate}}
	| MedlinePlus = a682542		| MedlinePlus = a682542
			| pregnancy_US = B
	| pregnancy_category = B (])
	| legal_status = Unscheduled;<br> ]		| legal_status = otc
	| routes_of_administration = Oral		| routes_of_administration = Oral
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	| bioavailability = 39.2%		| bioavailability = 39.2%
	| metabolism = ]		| metabolism = ]
	| elimination_half-life = 21.3 Hours		| elimination_half-life = 21.3 hours
	| excretion = ]		| excretion = ]
	<!--Identifiers-->		<!--Identifiers-->
			| IUPHAR_ligand = 6063
	| CASNo_Ref = {{cascite|correct|CAS}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 15686-51-8		| CAS_number = 15686-51-8
	| ATC_prefix = R06		| ATC_prefix = D04
	| ATC_suffix = AA04		| ATC_suffix = AA14
			| ATC_supplemental = {{ATC|R06|AA04}}
	| PubChem = 26987		| PubChem = 26987
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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	<!--Chemical data-->		<!--Chemical data-->
	| C=21 | H=26 | Cl=1 | N=1 | O=1		| C=21 | H=26 | Cl=1 | N=1 | O=1
	| molecular_weight = 343.9
	| smiles = Clc1ccc(cc1)(OCC2N(C)CCC2)(c3ccccc3)C		| smiles = Clc1ccc(cc1)(OCC2N(C)CCC2)(c3ccccc3)C
	| InChI = 1/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
	| InChIKey = YNNUSGIPVFPVBX-NHCUHLMSBN
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 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		| StdInChI = 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
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	| StdInChIKey = YNNUSGIPVFPVBX-NHCUHLMSSA-N		| StdInChIKey = YNNUSGIPVFPVBX-NHCUHLMSSA-N
	}}		}}
			<!-- Definition and medical uses -->
			'''Clemastine''', also known as '''meclastin''', is a first-generation ] antagonist (]) with ] properties (drying) and sedative side effects.<ref>{{cite web |url=https://www.drugbank.ca/drugs/DB00283 |title=Clemastine |website=DrugBank.com}}</ref> Like all first-generation antihistamines, it is sedating.<ref>{{cite web |url=https://www.pharmacytimes.com/p2p/perspectives-on-second-generation-otc-antihistamines |url-status=dead |archive-url=https://web.archive.org/web/20120501100507/http://www.pharmacytimes.com/p2p/Perspectives-on-Second-Generation-OTC-Antihistamines |archive-date=2012-05-01 |title=Perspectives on Second-Generation OTC Antihistamines |website=Pharmacy Times |date=2012-03-30}}</ref><ref>{{cite journal | vauthors = Krouse JH | title = Allergic rhinitis--current pharmacotherapy | journal = Otolaryngologic Clinics of North America | volume = 41 | issue = 2 | pages = 347–58, vii | date = April 2008 | pmid = 18328373 | doi = 10.1016/j.otc.2007.11.014 }}</ref>
			<!-- Society and culture -->
	'''Clemastine''', also known as '''meclastin''', is an ] and ]. Unlike ] or ], clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines.{{fact|date=September 2011}} Clemastine is also classified as an ] (i.e. it stops itching).
			Patented in 1960, it came into medical use in 1967.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=547 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA547 |language=en}}</ref>
			==Medical uses==
			Clemastine is used to relieve ] and ] symptoms, including sneezing; runny nose; and red, itchy, tearing eyes. Prescription strength clemastine is also used to relieve the itching and swelling of ].<ref>{{cite web |url=https://medlineplus.gov/druginfo/meds/a682542.html |title=Clemastine |website=MedlinePlus}}</ref>
			==Side effects==
		⚫	Overdosage symptoms are paradoxical, ranging from ] depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, ], ], loss of coordination, ], ], ], ], convulsions, ]s, and ]. This may be followed by ] depression and ]. Other common overdose symptoms include dry mouth, fixed dilated pupils, flushing of the face, and ]. In adults, overdose usually leads to CNS depression, ranging from drowsiness to ].<ref name="Drugs.com">{{cite web |title=Clemastine Side Effects: Common, Severe, Long Term |url=https://www.drugs.com/sfx/clemastine-side-effects.html |website=Drugs.com |access-date=13 December 2023 |date=23 January 2023}}</ref>
			Continuous and/or cumulative use of ] medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people.<ref>{{cite journal | vauthors = Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB | title = Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | journal = JAMA Internal Medicine | volume = 175 | issue = 3 | pages = 401–407 | date = March 2015 | pmid = 25621434 | pmc = 4358759 | doi = 10.1001/jamainternmed.2014.7663 | author5-link = Rebecca Hubbard }}</ref><ref>{{cite journal | vauthors = Carrière I, Fourrier-Reglat A, Dartigues JF, Rouaud O, Pasquier F, Ritchie K, Ancelin ML | title = Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study | journal = Archives of Internal Medicine | volume = 169 | issue = 14 | pages = 1317–1324 | date = July 2009 | pmid = 19636034 | pmc = 2933398 | doi = 10.1001/archinternmed.2009.229 }}</ref>
	==Pharmacology==		==Pharmacology==
	Clemastine is an antihistamine with ] and ] effects. Antihistamines competitively bind to ] receptor sites, thus reducing the neurotransmitter's effects. Effects of histamine (which are countered by antihistamines) include:		Clemastine is an antihistamine with ] and ] effects. Antihistamines competitively bind to ] receptor sites, thus reducing the neurotransmitter's effects.<ref>{{cite book | vauthors = Farzam K, Sabir S, O'Rourke MC | chapter = Antihistamines |date=2024 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK538188/ |access-date=2024-11-11 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30844215 }}</ref> Effects of histamine (which are countered by antihistamines) include:
	* Increased capillary permeability		* Increased capillary permeability
	* Increased capillary dilatation		* Increased capillary dilatation
	* ] (i.e. swelling)		* ] (i.e., swelling)
	* ] (Itch)		* ] (Itch)
	* Gastrointestinal/respiratory smooth muscle constriction		* Gastrointestinal/respiratory smooth muscle constriction
	Clemastine inhibits both the ] and ] effects of histamine. Depending on the dose, the drug can produce paradoxical effects, including CNS stimulation or depression.		Clemastine inhibits both the ] and ] effects of histamine. Depending on the dose, the drug can produce paradoxical effects, including CNS stimulation or depression.
	Most antihistamines exhibit some type of ] activity. Antihistamines act by competitively binding to H1- receptor sites, thus blocking the binding endogenous histamine. Antihistamines do not chemically inactivate or prevent the normal release of histamine.		Most antihistamines exhibit some type of ] activity. Antihistamines act by competitively binding to H<sub>1</sub>-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 ] (functional inhibitor of ]).<ref name="pmid18504571">{{cite journal |vauthors=Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P|title=Identification of novel functional inhibitors of acid sphingomyelinase|journal=PLOS ONE|volume=6|issue=8|pages=e23852|year=2011|doi=10.1371/journal.pone.0023852|pmid=21909365|pmc=3166082|bibcode=2011PLoSO...623852K |doi-access=free}}</ref>
	Clemastine is rapidly absorbed from the ] and peak plasma concentrations are attained in 2-4 hours.
		⚫	Clemastine is rapidly absorbed from the ] 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 ] and may interfere with other drugs metabolized by this isozyme.
⚫	===Mechanism of Action===
	Clemastine is a selective histamine H1 antagonist. It binds to the histamine H1 receptor, thus blocking the action of ] histamine, which leads to temporary relief of the negative symptoms caused by histamine.
		⚫	==Mechanism of action==
	===Metabolism===
			Clemastine is a selective histamine H<sub>1</sub> antagonist. It binds to the histamine H<sub>1</sub> receptor, thus blocking the action of ] histamine, which leads to temporary relief of the negative symptoms caused by histamine.<ref>{{Cite web |title=Clemastine - Mechanism, Indication, Contraindications, Dosing, Adverse Effect, Interaction, Hepatic Dose {{!}} Drug Index {{!}} Pediatric Oncall |url=https://www.pediatriconcall.com/drugs/clemastine/428 |access-date=2024-05-23 |website=www.pediatriconcall.com |language=en}}</ref>
⚫	Antihistamines are thought to be metabolized in the liver, mostly by mono-/didemethylation and glucuronide conjugation. It is an inhibitor of cytochrome P450 2D6 and may interfere with other drugs metabolized by this isozyme.
			==Society and culture==
	==Indications==
			Clemastine is an ] drug, and is available under many names and dosage forms worldwide. Most common brand name is '''Tavegyl'''.<ref>drugs.com Page accessed May 10, 2015</ref>
	Clemastine is indicated for use in treating allergic ], such as ], ], ] and ].
	===Availability===		==Research==
			Clemastine has been studied for its potential to treat several psychiatric and neurological disorders, including possibly promoting ] and myelin repair in conditions like ] (MS).<ref name="pmid37840769">{{cite journal |vauthors=Jiang S, Wang X, Cao T, Kang R, Huang L |title=Insights on therapeutic potential of clemastine in neurological disorders |journal=Frontiers in Molecular Neuroscience |volume=16 |pages=1279985 |date=2023 |pmid=37840769 |pmc=10568021 |doi=10.3389/fnmol.2023.1279985|doi-access=free }}</ref><ref name="Leigh 2023">{{cite web |last=Leigh |first=Suzanne |title=Can this Medication Reverse MS? Brain Biomarker Shows It Can |website=UCSF |date=12 June 2023 |url=https://www.ucsf.edu/news/2023/06/425566/can-medication-reverse-ms-brain-biomarker-shows-it-can |access-date=17 April 2024}}</ref> Early phase II clinical trials showed promise for promoting remyelination in patients with MS, with clemastine improving nerve conduction velocity in the optic nerve.<ref name="pmid38389586">{{cite journal |vauthors=Riboni-Verri G, Chen BS, McMurran CE, Halliwell GJ, Brown JW, Coles AJ, Cunniffe NG |title=Visual outcome measures in clinical trials of remyelinating drugs |journal=BMJ Neurology Open |volume=6 |issue=1 |pages=e000560 |date=2024 |pmid=38389586 |pmc=10882304 |doi=10.1136/bmjno-2023-000560}}</ref><ref name="pmid32145678">{{cite journal |vauthors=Moghaddasi M, Nabovvati M, Koushki A, Soltansanjari M, Sardarinia M, Mohebi N, Rabani S |title=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 |journal=Clinical Neurology and Neurosurgery |volume=193 |pages=105741 |date=June 2020 |pmid=32145678 |doi=10.1016/j.clineuro.2020.105741 }}</ref> 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.<ref name="Ciccone 2024">{{cite web |last=Ciccone |first=Isabella |title=Clemastine Arm of TRAP-MS Trial Halted Following Increased Disability Accumulation in Progressive Multiple Sclerosis |website=NeurologyLive |date=2 March 2024 |url=https://www.neurologylive.com/view/clemastine-arm-trap-ms-trial-halted-following-increased-disability-accumulation-progressive-ms |access-date=17 April 2024}}</ref><ref name="Dotinga 2024">{{cite web |last=Dotinga |first=Randy |title=Clemastine Tied to Worsening Symptoms in Multidrug MS Trial |website=Medscape |date=14 March 2024 |url=https://www.medscape.com/viewarticle/unexpected-finding-clemastine-fumarate-linked-worsening-2024a10004ss |access-date=17 April 2024}}</ref><ref name="Maia 2024">{{cite web |last=Maia |first=Margarida |title=ACTRIMS 2024: An antihistamine may speed MS disease progression |website=Multiple Sclerosis News Today |date=7 March 2024 |url=https://multiplesclerosisnewstoday.com/news-posts/2024/03/07/actrims-2024-antihistamine-may-speed-ms-disease-progression/ |access-date=17 April 2024}}</ref>
	Clemastine is an ] drug, and is available as a syrup (0.5 mg per 5mL) and tablet (1mg). It is sold in the United States under the brand name '''Tavist'''.
			==References==
	=== Brand Names in other countries ===
			{{reflist}}
	Brasil - In Brasil it is sold under the brand name of '''Agasten''' by Novartis.
	Germany - In Germany sold under the brand name '''Tavegil'''.
	Sweden - In Sweden it is sold under the brand name of '''Tavegyl''' and unlike the newer non-sedative antihistamines used for allergy, prescription only.
	Turkey - Sold under the brand name '''Tavegyl''' by Novartis.
	==Toxicity==
⚫	Overdosage symptoms are paradoxical, ranging from ] depression to stimulation. Stimulation is most common in children, and is usually followed by excitement, ], ], ], ], ], ], ] convulsions, ], and ]. This may be followed by ] and cardiovascular/respiratory arrest. Other common overdose symptoms include dry mouth, fixed dilated pupils, flushing of the face, and ]. In adults, overdose usually leads to CNS depression, ranging from drowsiness to coma.
	The oral LD<sub>50</sub> of clemastine in the rat and mouse is 3550 mg/kg and 730 mg/kg, respectively.
	==External links==		==External links==
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	{{Antipruritics}}		{{Antipruritics}}
	{{Cholinergics}}		{{Antihistamines}}
	{{Histaminergics}}		{{Hallucinogens}}
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			{{Histamine receptor modulators}}
			{{Muscarinic acetylcholine receptor modulators}}
			{{Sigma receptor modulators}}
			}}
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