アモキサピン 化学特性,用途語,生産方法
外観
白色～黄赤色～緑色粉末～結晶
溶解性
酢酸(100)に可溶氷酢酸(100)、クロロホルム、ジクロロメタンに可溶
用途
三環系抗うつ作用化合物です。 モノアミン神経伝達物質再取り込み阻害作用 を示します。
用途
三環系抗うつ作用化合物です。
モノアミン神経伝達物質再取り込み阻害作用
を示します。
効能
抗うつ薬, セロトニン・ノルアドレナリン再取り込み阻害薬
商品名
アモキサン (ファイザー)
説明
Amoxapine is a tetracyclic antidepressant with a wide range of pharmacological effects. It inhibits norepinephrine and serotonin reuptake, binding the respective transporters with K
d values of 16 and 58 nM. It has also been shown to act as either an antagonist or inverse agonist at serotonin 5-HT
2A,
2B,
2C,
3,
6,
7 (K
is = 1 and 2 nM for 5-HT
2A and 5-HT
2C, respectively), dopamine D
2,
3,
4 (K
d = 160 nM for D
2), α
1-adrenergic (K
d = 50 nM), and histamine H
1 (K
d = 25 nM) receptors.
化学的特性
Crystalline Solid
使用
Amoxapine is intended
more for relieving symptoms in patients with neurotic or situational depression. It has a
number of serious side effects.
定義
ChEBI: A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position.
一般的な説明
Consideration of the structure of amoxapine, 2-chloro-11-(1-piperazinyl)dibenz-[b,f] [1,4]oxazepine (Asendin), reinforcesthe fact that many antidepressants are very closelyrelated to antipsychotics. Indeed, some, including amoxapine,have significant effects at D
2 receptors. The Nmethyl–substituted relative of amoxapine is the antipsychoticloxapine (Loxitane). The 8-hydroxy metabolite ofamoxapine is reportedly active as an antidepressant and asa D
2 receptor blocker.
作用機序
Additionally, it is the N-desmethyl metabolite
of the antipsychotic loxapine. Amoxapine differs structurally from the other secondary TCAs in that it has both
a nitrogen and an oxygen atom in its 7-membered central ring and a piperazinyl ring rather than a
propylamino side chain attached to the central ring.Amoxapine is a less potent inhibitor of neuronal NE reuptake compared with the other secondary TCAs, with a
mechanism of action similar to that of desipramine.
薬物動態学
Amoxapine shares the toxic potentials of the TCAs, and
the usual precautions of TCA administration should be observed. Amoxapine resembles the atypical antipsychotic drugs in its intermediate affinity as an antagonist of dopamine-2 and of 5-HT2 receptors.
Amoxapine is rapidly and almost completely absorbed from the gastrointestinal (GI) tract. Amoxapine and its 8-hydroxyamoxapine metabolite have been detected in human milk at concentrations below steady-state therapeutic concentrations.
薬理学
The antidepressant action of amoxapine is comparable to that of imipramine and amitriptyline. It exhibits antagonistic activity on dopamine (D2) receptors.
臨床応用
Amoxapine is a dibenzoxazepine TCA with antidepressant and antipsychotic effects that has shown
therapeutic effectiveness in patients with delusional depression.
安全性プロファイル
Poison by ingestion andintraperitoneal routes. Human systemic effects byingestion: acute renal failure, acute tubular necrosis, BPlowering, coma, convulsions, decreased body temperature,EKG changes, excitement, fasciculations, heart ratechanges, hype
代謝
Amoxapine has the shortest elimination
time (~8 hours) of the secondary TCAs. It is metabolized in the liver principally to 8-hydroxyamoxapine and to
7-hydroxyamoxapine. Both of these metabolites are pharmacologically active and have half-lives of 30 and 6.5
hours, respectively. The hydroxylation of amoxapine is inhibited by ketoconazole, suggesting the involvement
of CYP3A4."
アモキサピン 上流と下流の製品情報
原材料
準備製品