Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/16 20:58:26」(JST)

wiki en

Clemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines.^{[citation needed]} Clemastine is also classified as an antipruritic (i.e. it stops itching).

Pharmacology [edit]

Clemastine is an antihistamine with anticholinergic and sedative effects. Antihistamines competitively bind to histamine receptor sites, thus reducing the neurotransmitter's effects. 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 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).^[1]

Clemastine is rapidly absorbed from the gastrointestinal tract and peak plasma concentrations are attained in 2-4 hours.

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..

Metabolism [edit]

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.

Indications [edit]

Clemastine is indicated for use in treating allergic rhinitis, such as sneezing, rhinorrhea, pruritus and lacrimation.

Availability [edit]

Clemastine is an OTC 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.

Brand names in other countries [edit]

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 [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, incoordination, 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.

The oral LD₅₀ of clemastine in the rat and mouse is 3550 mg/kg and 730 mg/kg, respectively.

References [edit]

^ 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 (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.

External links [edit]

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

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 授乳中の薬剤使用の原則 principles of medication use during lactation
2. 成人における亜急性および慢性咳嗽の治療 treatment of subacute and chronic cough in adults
3. 患者情報：アレルギー性鼻炎（季節性アレルギー）（詳細） allergic rhinitis seasonal allergies beyond the basics
4. 患者情報：成人における慢性咳嗽（詳細） chronic cough in adults beyond the basics

English Journal

Treatment of angiotensin receptor blocker-induced Angioedema: A case series.

Strassen U1, Bas M1, Hoffmann TK2, Knopf A2, Greve J2.
The Laryngoscope.Laryngoscope.2015 Jul;125(7):1619-23. doi: 10.1002/lary.25163. Epub 2015 Feb 3.
BACKGROUND: Angiotensin II receptor antagonists have been proposed as a replacement therapy after the occurrence of either an angiotensin converting enzyme (ACE) inhibitor-induced angioedema or cough. However, recent studies indicate that angioedema is associated with elevated bradykinin levels in a
PMID 25646708

A randomized trial of icatibant in ACE-inhibitor-induced angioedema.

Baş M1, Greve J, Stelter K, Havel M, Strassen U, Rotter N, Veit J, Schossow B, Hapfelmeier A, Kehl V, Kojda G, Hoffmann TK.
The New England journal of medicine.N Engl J Med.2015 Jan 29;372(5):418-25. doi: 10.1056/NEJMoa1312524.
BACKGROUND: Angioedema induced by treatment with angiotensin-converting-enzyme (ACE) inhibitors accounts for one third of angioedema cases in the emergency room; it is usually manifested in the upper airway and the head and neck region. There is no approved treatment for this potentially life-threat
PMID 25629740

Clemastine Confers Neuroprotection and Induces an Anti-Inflammatory Phenotype in SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis.

Apolloni S1, Fabbrizio P, Parisi C, Amadio S, Volonté C.
Molecular neurobiology.Mol Neurobiol.2014 Dec 9. [Epub ahead of print]
Mutations in the Cu2+/Zn2+ superoxide dismutase 1 (SOD1) gene underlie 14-23 % of familial and 1-7 % of sporadic cases of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease characterized by a specific loss of motor neurons in the brain and spinal cord. Neuroinflammation a
PMID 25482048

Japanese Journal

ラマトロバンと抗ヒスタミン薬の併用効果

成田慎一郎,白崎英明,黒瀬誠 [他],小林一豊,氷見徹夫
耳鼻咽喉科臨床 95(6), 653-658, 2002-06-01
… We investigated the effects of combination therapy with thromboxane A2 receptor antagonist (TxA2 RA: Ramatroban) and an antihistamine (Clemastine Fumarate) in patients with perennial allergic rhinitis. … There was no significant difference in the three groups: combination group (n=20), the TxA2 RA (only Ramatroban) group (n=18) and the antihistamine (only Clemastine Fumarate) group (n=9) in terms of global improvement rating. …
NAID 10008575190

A Case of Anaphylaxis Induced by Lafutidine.

辻本達寛,飯岡弘伊,浪崎正,豊川泰勲,鶴薗卓也,松村吉庸,福井博
日本救急医学会雑誌 13(7), 385-388, 2002
… He had been treated with lafutidine, cefotiam hydrochloride, serrapeptase, pranoprofen, aspirin, acetaminophen, clemastine fumarate, scopolia extract and sodium azulenesulfonate for tonsilitis at another hospital. …
NAID 130003437616

プランルカストと抗ヒスタミン薬の併用効果

成田慎一郎,白崎英明,渡辺一正,菊地一也,黒瀬誠,小林一豊,氷見徹夫
耳鼻咽喉科臨床 94(12), 1131-1138, 2001-12-01
… We investigated the effects of the combination therapy of leukotriene receptor antagonist (Pranlukast) and an antihistamine (Clemastine Fumarate) on patients with perennial allergic rhinitis. … There was no significant difference between the combination (Pranlukast and Clemastine Fumarate) group (n=14) and the single (only Pranlukast) group (n=14) in terms of global improvement rating. …
NAID 10008098537

「クレマスチン」

Clemastine
Systematic (IUPAC) name
	(2R)-2-{2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl}-1-methylpyrrolidine
Clinical data
Trade names	Tavist-1
AHFS/Drugs.com	monograph
MedlinePlus	a682542
Pregnancy cat.	B (USA)
Legal status	Unscheduled;; OTC
Routes	Oral
Pharmacokinetic data
Bioavailability	39.2%
Metabolism	Hepatic
Half-life	21.3 Hours
Excretion	Renal
Identifiers
CAS number	15686-51-8
ATC code	D04AA14 R06AA04
PubChem	CID 26987
DrugBank	DB00283
ChemSpider	25129
UNII	95QN29S1ID
KEGG	D03535
ChEBI	CHEBI:3738
ChEMBL	CHEMBL1626
Chemical data
Formula	C21H26ClNO
Mol. mass	343.9
	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 ; Key:YNNUSGIPVFPVBX-NHCUHLMSSA-N ;
(what is this?) (verify);