LOXAPINE

Uses

Tranquilizer (minor).

Uses

Loxapine is a more expressed, active antipsychotic than chlorpromazine. Its sedative effect is inferior to that of chlorpromazine. Indications for its use and side effects correspond with those of phenothiazine derivatives. Loxapine is used for treating psychotic disturbances, in particular cases of chronic and severe schizophrenia.

brand name

Loxitane-C Oral Suspension [as hydrochloride] (Wyeth-Ayerst); Loxitane Intramuscular [as hydrochloride] (Wyeth-Ayerst).

General Description

A dibenzoxazepine derivative in use is loxapinesuccinate, 2-chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f ][1,4]oxazepine succinate (Daxolin). The structural relationshipto the phenothiazine antipsychotics is apparent. Examplesin this group are clothiapine, metiapine, zotepine, and others.They have electron-withdrawing groups at position 2, relativelyclose to the side-chain nitrogen atoms. Loxapine, an effectiveantipsychotic, blocks D₂-type receptors and has side effectssimilar to those reported for the phenothiazines. Itsmetabolism involves aromatic hydroxylation to give severalphenolic metabolites that have higher affinity for D2 receptorsthan the parent. It is also N-demethylated to yield amoxapine(an antidepressant drug), which inhibits norepinephrine (NE)neurotransporter to block neuronal NE reuptake.

Clinical Use

Typical antipsychotic:
Treatment of mild to moderate agitation in schizophrenia or bipolar disease

Synthesis

Loxapine, 2-chloro-11-(4-methyl-1-piperazinyl)dibenz [b,f][1,4]exazepine (6.5.3), which is synthesized from 2-(4-chlorophenoxy)anyline. Acylation of the resulting product using ethylchloroformate forms N-ethoxycarbonyl-2-(4-chlorophenoxy)aniline (6.5.2). Treatment of this product with a mixture of phosphorous oxychloride and phosphorous anhydride gives loxapine (6.5.3) [53–55].

Raw materials

Preparation Products