Amoxapin Chemische Eigenschaften,Einsatz,Produktion Methoden
R-S?tze Betriebsanweisung:
R22:Gesundheitssch?dlich beim Verschlucken.
S-S?tze Betriebsanweisung:
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
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.
Chemische Eigenschaften
Crystalline Solid
Verwenden
Amoxapine is intended
more for relieving symptoms in patients with neurotic or situational depression. It has a
number of serious side effects.
Definition
ChEBI: A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position.
Allgemeine Beschreibung
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.
Mechanism of action
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.
Pharmakologie
The antidepressant action of amoxapine is comparable to that of imipramine and amitriptyline. It exhibits antagonistic activity on dopamine (D2) receptors.
Pharmakokinetik
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.
Clinical Use
Amoxapine is a dibenzoxazepine TCA with antidepressant and antipsychotic effects that has shown
therapeutic effectiveness in patients with delusional depression.
Sicherheitsprofil
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
Stoffwechsel
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."
Amoxapin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
