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 D
2-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].
