JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: A review of its behavioural properties

Jacques Bruhwyler*, Jean François Liégeois, Jack Bergman, Galen Carey, Andrew Goudie, Anita Taylor, Herbert Meltzer, Jacques Delarge, Joseph Géczy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The search for an improved clozapine-like compound has resulted in the selection of a new molecule: JL13 (5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate). Like clozapine, JL13 did not antagonize apomorphine-induced stereotypy and did not produce catalepsy but antagonized apomorphine-induced climbing in rodents (ID50 = 3.9 mg kg-1 s.c.). It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse (ID50 = 4.4 mg kg-1 i.p.). JL13, like clozapine, was able to antagonize (±)-DOI-induced head-twitches in the mouse (ID50 = 2.0 mg kg-1 i.p.). In the open-field test in the rat and forced swimming test in the mouse a high similarity was noted between the two drugs in the same range of doses. In a complex temporal regulation schedule in the dog, JL13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats trained to discriminate clozapine, JL13 (10 mg kg-1 i.p.) induced a high level of generalization (70%) to clozapine. In a drug discrimination procedure in the squirrel monkey, JL13 (3-10 mg kg-1 i.m.) produced a full substitution of clozapine. On the basis of these preclinical data, it is thus predicted that JL13 would be a promising atypical antipsychotic drug.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalPharmacological Research
Volume36
Issue number4
DOIs
StatePublished - Oct 1997

Keywords

  • Atypical antipsychotic
  • Behavioural pharmacology
  • Clozapine
  • JL13

ASJC Scopus subject areas

  • Pharmacology

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