JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity, increases extracellular dopamine in the prefrontal cortex, but not in the striatum and the nucleus accumbens of rats.
In behavioral and receptor binding studies, 5-(4-methylpiperazin-1-yl)-8-chloro-pyridol[2,3b] [1,5]benzoxazepine (JL13) shows an atypical antipsychotic profile. We used microdialysis in awake rats to study the effects of various intraperitoneal doses of JL13 on extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens and striatum. JL13 at 20 mg/kg and 40 mg/kg dose-dependently raised extracellular dopamine (234% and 434% of basal levels at peak, respectively) in the prefrontal cortex whereas lower doses (5 mg/kg and 10 mg/kg) had no effect. Extracellular concentrations of dihydroxyphenylacetic acid and homovanillic acid were also significantly increased in the prefrontal cortex of rats given 40 mg/kg JL13 (310% and 230% of basal levels, respectively). At 20 mg/kg and 40 mg/kg JL13 did not affect the extracellular concentrations of dopamine and its metabolites in the striatum and nucleus accumbens. The mechanisms by which JL13 increases cortical dopamine release and the significance for potential antipsychotic efficacy are discussed.
Invernizzi
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Laboratory of Neuropharmacology, Milan, Italy.
Garavaglia
C
C
Samanin
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D051381:Rats
D014150:Antipsychotic Agents; D002316:Cardiotonic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; C108260:JL 13 compound; D003024:Clozapine; D004298:Dopamine; D006719:Homovanillic Acid