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

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
J. BruhwylerJ Géczy

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 pr...Continue Reading

Citations

Sep 18, 2007·Journal of Molecular Neuroscience : MN·Frank I TaraziJean-François Liégeois
Sep 10, 2009·European Journal of Pharmacology·Katia LombardoFranco Borsini
Mar 3, 2007·Journal of Psychopharmacology·Andrew J GoudieHarry R Sumnall
Jul 1, 2006·Journal of Neuroscience Research·Taylor Moran-GatesFrank I Tarazi
Jan 16, 2007·Behavioural Pharmacology·Andrew J GoudieHarry R Sumnall
Feb 22, 2003·CNS Drug Reviews·Bart A Ellenbroek, Jean-François Liégeois

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