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クレマスチンフマル酸塩

Clemastine Fumarate

HCID 5281069
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基本情報概要名称と識別子物性安全と法規制化学と産業関連反応化合物ノート
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基本情報

CAS
14976-57-9
標準SMILES
CN1CCC[C@@H]1CCO[C@](C)(c1ccccc1)c1ccc(Cl)cc1.O=C(O)/C=C/C(=O)O
InChIKey
PMGQWSIVQFOFOQ-YKVZVUFRSA-N
分子式
C25H30ClNO5
平均分子量
460 g/mol
単同位体質量
459.1812508

概要

Clemastine fumarate is the fumaric acid salt of clemastine. An antihistamine with antimuscarinic and moderate sedative properties, it is used for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions. It has a role as a H1-receptor antagonist, a muscarinic antagonist, an anti-allergic agent and an antipruritic drug. It contains a clemastine.

名称と識別子

優先名称
Clemastine Fumarate
IUPAC
(E)-but-2-enedioic acid;(2R)-2-[2-[(1R)-1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine
現地名
クレマスチンフマル酸塩
英語名
Clemastine fumarate
分子式
C21H26ClNO.C4H4O4
分子量
459.96

名称と別名

CLEMASTINE FUMARATE14976-57-9AgastenTavistMecloprodineAloginanXolaminClemastine hydrogen fumarateAlphaminAnhistanClemanilFuluminol
名称をさらに表示
クレマスチンフマル酸塩[2R,(+)]-2-[2-[[(R)-1-(p-クロロフェニル)-1-フェニルエチル]オキシ]エチル]-1-メチルピロリジン·(E)-2-ブテン二酸マルスチンマスレチンフルミノールマレルミンFクレマニルベナンジール(2R)-2-[2-[(R)-1-(4-クロロフェニル)-1-フェニルエトキシ]エチル]-1-メチルピロリジン·(E)-2-ブテン二酸テルギンGタベジール[2R,(+)]-2-[2-[[(R)-1-(p-クロロフェニル)-1-フェニルエチル]オキシ]エチル]-1-メチルピロリジン·フマル酸塩キソラミンアラギールインベスタンクレ·ママレットキノトミンフマル酸クレマスチンハイニュースクレマスチンフマル酸塩 (JP17)hs592Alagyltavegiltavegyltrabest
InbestanKinotominLacretinMarsthineMasletineLecasolPiloralReconin

物性

構造計算による物性

極性表面積
87.1 Ų
水素結合供与体数
2
水素結合受容体数
6
回転可能結合数
8
重原子数
32
形式電荷
0
複雑度
495

実験および物理化学的性質

OdorOdorless
Color/FormColorless to faintly yellow crystalline powder
SolubilityVery slightly soluble in water and sparingly soluble in alcohol.
Human Drugs · 2 件

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Boiling Point154 °C at 0.02 mm Hg
Melting Point177-178 °C
Other Experimental Properties154 °C at 0.02 mm Hg (free base)

物理化学的性質

融点
158 · 158-162°C
比旋光度
21 · D21 +16.9° (methanol)
沸点
154 °C · 154°C (rough estimate)
比重(密度)
1.0247 · 1.0247 (rough estimate)
屈折率
1.579 · 1.5790 (estimate)
貯蔵温度
2 · 2-8°C
溶解性
5 mg/mL · DMSO: 可溶5mg/mL (透明溶液; 加温)

安全と法規制

安全情報は参考情報です。供給元の安全データシート（SDS）、適用法令、専門家による評価に代わるものではありません。

GHS分類

GHS Classification · 5 件

This chemical does not meet GHS hazard criteria for 66.7% (12 of 18) of all reports.

Warning

H400 (22.2%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

P273, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 18 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

危険有害性情報

FDA Requirements · 2 件

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl clemastine fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From the Prescription Drug Product List/

Hazard Classes and CategoriesAquatic Acute 1 (22.2%)

毒性情報

Body BurdenFollowing oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 ug/ml occurred 20 hours after the last dose of the drug.
Milk ConcentrationsFollowing oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 ug/ml occurred 20 hours after the last dose of the drug.
Human Toxicity Excerpts

化学と産業

薬理情報

Mechanism of Action · 1 件

Inhibitory effects of various histamine receptor-blocking agents including antiallergic agents on metabolic activations of neutrophils were examined by measuring leukotrienes (C4, D4 and E4) formation, arachidonic acid release and superoxide generation. The stimulation of neutrophils by calcium ionophore causes the production of leukotrienes concomitantly with the release of arachidonic acid from the cells and these were effectively diminished with a variety of antihistaminic agents. Almost all the histamine H1 receptor-blocking drugs studied here showed as inhibitors of the metabolic activations of neutrophils, although the degree was dependent on the drug concentrations. The order of potency of the inhibitory effects on the arachidonic acid release were: homochlorcyclizine, clemastine, and azelastine (IC50 < 20 microM) greater than oxatomide (IC50 < 60 microM) and diphenylpyraline greater than triprolidine, meclizine, diphenhydramine (IC50 > 100 microM). The superoxide generation from neutrophils activated by phorbol 12-myristate 13-acetate was also effectively inhibited by these agents, but generally lower concentrations were required to obtain the same degrees of effects. These results indicated that some of the histamine H1 receptor-blocking drugs, such as clemastine and homochlorcyclizine, may act as inhibitors of formation of leukotrienes at the locus of inflammation.

Metabolism/Metabolites · 2 件

The exact metabolic fate of clemastine is not clearly established, but the drug appears to be extensively metabolized. Clemastine and its metabolites are eliminated principally in urine.

Time to peak concentration: 2-4 hr

MeSH Pharmacological Classification · 3 件

Agents, usually topical, that relieve itching (pruritus).

Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.

Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)

関連反応

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化合物ノート

読み込み中…

このページの内容基本情報概要名称と識別子物性安全と法規制化学と産業関連反応化合物ノート

データベース識別子

CAS
14976-57-9、15686-51-8
PubChem CID
5281069
DTXSID
DTXSID6047785
ChEMBL
CHEMBL1200795
ChEBI
CHEBI:3739
UNII
19259EGQ3D
EC Number
239-055-2
外見
粉
色
白からベージュ
InChIKey
PMGQWSIVQFOFOQ-YKVZVUFRSA-N
SMILES
[C@@](C)(OCC[C@H]1CCCN1C)(C1C=CC=CC=1)C1=CC=C(Cl)C=C1.C(/C(=O)O)=C\C(=O)O |&1:0,5,r|
CAS データベース
14976 · 14976-57-9(CAS DataBase Reference)

化学的性質

化学的特性White Solid

· 2 件

Usual therapeutic doses of clemastine interfere with color vision.

Drowsiness, irritability, refusal to feed, and high-pitched cry occurred in one breast-fed infant (10 weeks of age) of a women who received 2.68 mg of clemastine fumarate daily for 3 days.

Drug Induced Liver Injury · 6 件

Drug Induced Liver Injury Rank (DILIrank 2.0)

Clemastine fumarate

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

Non-Human Toxicity Excerpts · 3 件

Reproduction studies in rats and rabbits using oral clemastine fumarate dosages up to 312 and 188 times the usual human adult dosage, respectively, have not revealed evidence of harm to the fetus. Reproduction studies in rats and rabbits using oral clemastine fumarate and phenylpropanolamine hydrochloride in a fixed combination ratio of 1:49 and at oral dosages up to 100 (in rats) and 67 (in rabbits) times the usual human dosage have not revealed evidence of teratogenic effects. Impaired maternal weight gain and death at 33 times the usual human dosage, and reduced fetal weight and slight increases in preimplantation loss and prenatal death at 100 times the usual human dosage were attributed to phenylpropanolamine in rats. Increased maternal death at dosages 20 and 67 times the usual human dosage, and maternal weight loss and a slight (but within normal limits) increase in prenatal death at a dosage 67 times the usual human dosage were attributed to phenylpropanolamine in rabbits.

Oral dosage of clemastine fumarate 312 times the usual human adult dosage have decreased mating ability in male rats, but dosages 156 times the usual human adult dosage had no effect on mating.

There was no evidence of carcinogenesis in rats receiving clemastine fumarate at an oral dosage of 84 mg/kg (about 500 times the usual human adult dosage) for 2 years or in mice receiving 206 mg/kg (about 1300 times the usual human adult dosage) for 85 weeks. The carcinogenic potential of clemastine fumarate in fixed combination with phenylpropanolamine has not been determined.

Antidote and Emergency Treatment · 1 件

Since there is no specific antidote for overdose with antihistamines, treatment is symptomatic and supportive with possible utilization of the following: 1) Induction of emesis (syrup of ipecac recommended); however, precaution against aspiration necessary, especially in infants and children. 2) Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient unable to vomit within three hours of ingestion. 3) Saline cathartics (milk of magnesia) are sometimes used. 4) Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure. 5) Oxygen and intravenous fluids. 6) Precaution against use of stimulants (analeptic agents) because they may cause seizures. /Antihistamines/

Non-Human Toxicity Values · 4 件

LD50 Mouse oral 730 mg/kg

LD50 Mouse iv 43 mg/kg

LD50 Rat oral 3550 mg/kg

LD50 Rat iv 82 mg/kg

法規制情報

FDA Requirements · 2 件

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl clemastine fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From the Prescription Drug Product List/

安全データ

wgk
3
rtecs
UY0704600
毒性
LD50 in mice, rats (mg/kg): 730, 3550 orally; 43, 82 i.v. (Weimann)
hs_code
2933992600
ストレージクラス
11 - Combustible Solids
有毒物質データの
14976-57-9(Hazardous Substances Data)
Absorption, Distribution and Excretion · 4 件

In 12 healthy subjects given clemastine fumarate by mouth peak plasma concentrations occurred after 3 to 5 hr. After intravenous injection in 3 subjects a rapid decline in plasma concentration during the first 30 minutes occurred followed by a slow rise to peak concentration 2 to 3 hours after administraton. In 5 subjects given clemastine fumarate the ability to inhibit histamine flares correlated well with plasma concentation.

Clemastine fumarate is rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations of the drug are attained within 2-5 hours after a single oral dose. Following oral administration of clemastine fumarate, the antihistaminic effect of the drug (as measured by suppression of the wheal response induced by intradermal injection of histamine) is maximal within 5-7 hours and persists for 10-12 and, in some individuals, up to 24 hours.

Distribution of clemastine into human body fluids and tissues has not been fully characterized, but the drug has been shown to distribute into milk. Following oral administration of 2.68 mg of clemastine fumarate daily for 3 days in one nursing woman, a milk clemastine concentration of about 5-10 ug/ml occurred 20 hours after the last dose of the drug and was about 25-50% of the stimultaneous maternal plasma drug concentration; clemastine was undetectable in milk 6 days after discontuance of the drug.

Clemastine and its metabolites are eliminated principally in urine.

用途と製造

Uses · 2 件

MEDICATION

Use (kg; approx.) in Germany (2009): >10

Formulations/Preparations · 2 件

Oral; tablets extended release core (phenylpropanolamine hydrochloride only), film-coated; 1.34 mg with phenylpropanolamine hydrochloride 75 mg, Tavist-D (with povidone), Sandoz. /Clemastine fumurate combination/

Oral solution; 0.67 mg/5 ml Tavist Syrup (with alcohol 5.5%, parabens, and propylene glycol), Sandoz. Tablets; 1.34 mg, Tavist-1 (with povidone; scored), Sandoz; 2.68 mg Tavist (with povidone; scored), Sandoz.

応用分野 · 4 件

用途プロパノールアミン誘導体で す。抗ヒスタミン作用を示します。

用途薬理研究用。

使用Clemastine fumarate is a selective histamine H1 receptor antagonist (Ki = 0.26 nM) that also displays high affinity for muscarinic receptors (Ki = 16 nM). It has also recently been identified as a positive allosteric modulator of P2X7 receptor signaling. Clemastine fumarate has long been used to inhibit histamine-induced bronchoconstriction in asthma and airway hyperresponsive studies.

一般的な説明Dextrorotatory clemastine, R,R-2[2[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1- methylpyrrolidine hydrogen furnarate (1:1) (Tavist), has two chiral centers, each of which has the (R) absolute configuration. A comparison of the activities of the enantiomers indicates that the asymmetric center close to the terminal side chain nitrogen is of lesser importance to antihistaminic activity. This member of the ethanolamine series is characterized by a long duration of action, with an activity that reaches a maximum in 5 to 7 hours and persists for 10 to 12 hours. It is well absorbed when administered orally, and it is excreted primarily in the urine. The side effects are those usually encountered with this series of antihistamines. Clemastine is closely related to chlorphenoxamine, which is used for its central cholinergic-blocking activity. Therefore, it is not surprising that clemastine has significant antimuscarinic activity.

上流・下流製品情報

上流原料

ナトリウムアミドフマル酸

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補足説明 · 1 件

定義ChEBI: The fumaric acid salt of clemastine. An antihistamine with antimuscarinic and moderate sedative properties, it is used for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin condi ions.