Амоксапин

Описание

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 D₂, ₃, ₄ (K_d = 160 nM for D₂), α₁-adrenergic (K_d = 50 nM), and histamine H₁ (K_d = 25 nM) receptors.

Химические свойства

Crystalline Solid

Использование

Amoxapine is intended more for relieving symptoms in patients with neurotic or situational depression. It has a number of serious side effects.

Определение

ChEBI: A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position.

Общее описание

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 D₂ receptors. The Nmethyl–substituted relative of amoxapine is the antipsychoticloxapine (Loxitane). The 8-hydroxy metabolite ofamoxapine is reportedly active as an antidepressant and asa D₂ receptor blocker.

Механизм действия

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.

Фармаколо?гия

The antidepressant action of amoxapine is comparable to that of imipramine and amitriptyline. It exhibits antagonistic activity on dopamine (D2) receptors.

Фармакокине?тика

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.

Клиническое использование

Amoxapine is a dibenzoxazepine TCA with antidepressant and antipsychotic effects that has shown therapeutic effectiveness in patients with delusional depression.

Профиль безопасности

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

Метаболизм

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."