クロザピン

危険有害性情報のコード(GHS)

• 絵表示(GHS)

  

• 注意喚起語

  Danger

• 危険有害性情報

  H301：飲み込むと有毒

  H341：遺伝性疾患のおそれの疑い

  H361：生殖能または胎児への悪影響のおそれの疑い

• 注意書き

  P201：使用前に取扱説明書を入手すること。

  P202：全ての安全注意を読み理解するまで取り扱わないこ と。

  P264：取扱い後は皮膚をよく洗うこと。

  P264：取扱い後は手や顔をよく洗うこと。

  P270：この製品を使用する時に、飲食または喫煙をしないこ と。

  P280：保護手袋/保護衣/保護眼鏡/保護面を着用するこ と。

  P301+P310：飲み込んだ場合：直ちに医師に連絡すること。

クロザピン 価格

MSDS Information

• 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine

クロザピン 化学特性,用途語,生産方法

• 外観

  ごくうすい黄色〜黄色, 結晶〜粉末

• 溶解性

  メタノールに溶ける。

• 用途

  セロトニン5-HT2A 受容体阻 害作用を示します。ドーパミンD2 受容体に 対する親和性が低く、セロトニン5-HT2A 受 容体及びドーパミンD4 受容体に対して高い 親和性を示します。D2 受容体遮断作用に依存 せず、中脳辺縁系への選択的抑制作用を示す と考えられています。

• 効能

  統合失調症治療薬

• 商品名

  クロザリル (ノバルティスファーマ)

• 化学的特性

  Yellow Crystalline Solid

• 来歴

  The development of clozapine began in the late 1950s by researchers at the Swiss pharmaceutical company Wander. In the early 1960s, a team led by Fritz Hunziker and Jörg Schmutz synthesized the compound, a tricyclic dibenzoxazine. Clozapine's pharmacological properties differed significantly from traditional antipsychotics; it possessed potent antipsychotic activity and exhibited almost no extrapyramidal symptoms. Clozapine was approved in Europe for the treatment of schizophrenia in 1972 and in the United States in 1975. However, subsequent cases of agranulocytosis—particularly the fatal case in Finland—led to its withdrawal from the US market in 1975. Throughout the 1980s, a research team led by John Kane and Herbert Meltzer demonstrated through rigorous clinical trials that clozapine had a significant therapeutic effect on treatment-resistant schizophrenia unresponsive to traditional antipsychotics. This evidence prompted the US Food and Drug Administration (FDA) to conditionally re-approve its marketing in 1989, but only under the condition of using a rigorous blood monitoring system.

• 使用

  Clozapine is a neuroleptic, which expresses antipsychotic and sedative action. It does not cause general depression and extrapyramidal disorders. It is used for severe and chronic forms of schizophrenia, maniacal conditions, manic-depressive psychosis, psychomotor excitement, and various other psychotic conditions.

• 定義

  ChEBI: A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatr c disorders like schizophrenia.

• 世界保健機関（WHO）

  Clozapine, a tricyclic neuroleptic, was introduced in 1972 for the treatment of psychosis. In 1975 its use was associated with cases of agranulocytosis, particularly in Finland. These cases, which included several fatalities, resulted in the withdrawal of the drug in some countries. However, clozapine remains available in at least 30 countries, in some cases only on special request, for the treatment of severe psychotic disorders unresponsive to other neuroleptics provided that close monitoring of the blood count is feasible. In 1989, it was introduced in the United States for the treatment of severe schizophrenia. Lately, the use of clozapine in the United Kingdom has been associated with convulsions. (Reference: (WHODIB) WHO Drug Information Bulletin, 2: 10, , 1977)

• 一般的な説明

  Clozapine, 8-chloro-11-(4-methyl-1-piperazinyl)5H-dibenzo[b,e] [1,4] diazepine (Clozaril), is a yellowcrystalline powder that is only slightly soluble in water. Withthe introduction of clozapine, a different pharmacological antipsychotics.106 Unlike typical antipsychotics, clozapine is largelydevoid of EPS. The lack of EPS with this compound waspostulated to be caused by its preferential binding tomesolimbic rather than striatal DA receptors.Furthermore,clozapine was shown to exhibit potent affinity for 5-HT2Areceptors.
  DMCZ shows partial agonism at D₂ and D₃ receptors andexhibits a distinctly different pharmacological profile comparedwith clozapine and other atypical antipsychotics.Unlike clozapine, which is a potent M₁ muscarinic antagonist,DMCZ is a potent M₁ agonist. Agonism at muscarinicreceptors has been proposed to be useful for impaired cognitionin schizophrenia. Burnstein et al.found thatDMCZ acted as a partial agonist at DA D₂ and D₃ receptors.These investigators suggested that the low incidence of EPSassociated with clozapine may be caused by the partial agonismof DMCZ at D₂ and D₃ receptors. Thus, DMCZ maybe of interest as an atypical antipsychotic with an improvedside effect profile compared with clozapine.

• 生物活性

  Atypical antipsychotic drug, with a much lower tendency to cause extrapyramidal side effects than conventional neuroleptics. Displays a broad range of pharmacological actions; the antipsychotic effects are thought to be mediated principally by 5-HT 2A/2C and dopamine receptor blockade (K i values are 21, 170, 170, 230 and 330 nM for D 4 , D 3 , D 1 , D 2 and D 5 receptors respectively).

• 臨床応用

  Although clozapine demonstrates a favorable pharmacologicalprofile compared with typical antipsychotics, its useis restricted by a relatively high incidence of agranulocytosis.The exact mechanism for the cause of agranulocytosishas not been confirmed, but a highly reactive nitrenium ionthat is formed by the action of hepatic enzymes appears tobe involved.The mean elimination half-life of clozapine following a single 75-mg dose is 8 hours. Because of severaladverse effects, clozapine is only used in refractory casesof schizophrenia. Individuals with a history of seizures orpredisposed to seizures should be cautioned when takingclozapine. Similar to other atypical antipsychotic agents,clozapine causes an increased risk of mortality in elderly individualswith dementia-related psychoses.

• 副作用

  A serious drawback to the use of clozapine, however, is the potentially fatal agranulocytosis that is reported to occur in 1 to 2% of unmonitored patients, necessitating weekly white blood cell counts for at least the first 6 months of pharmacotherapy.

• 代謝

  Clozapine is orally active and metabolized mainly by CYP3A4 to inactive desmethyl, hydroxyl, and N-oxide derivatives, with a half-life of approximately 12 hours. Clozapine has relatively low affinity for brain dopamine D1 and D2 receptors (moderate affinity for D4) in comparison to its affinity at adrenergic α1 and α2, histamine H1, muscarinic M1 and serotonin 5-HT2A receptors.

クロザピン 上流と下流の製品情報

クロザピン 生産企業

Global(568)Suppliers

クロザピン スペクトルデータ(¹HNMR)

5786-21-0, クロザピン キーワード