Long-term effects of JL 13, a potential atypical antipsychotic, on rat dopamine and serotonin receptor subtypes.
Changes in dopamine (DA) D(1), D(2), D(3), and D(4) receptors and serotonin 5-HT(1A) and 5-HT(2A) receptors in rat forebrain regions were autoradiographically quantified after continuous infusion of JL 13 [(5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate] for 28 days with osmotic minipumps and compared with the effects of other typical (fluphenazine) and atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from previous studies. Similar to other typical and atypical antipsychotics, JL 13 increased labeling of D(2) receptors in medial prefrontal cortex (MPC) and hippocampus (HIP) and D(4) receptors in nucleus accumbens (NAc), caudate-putamen (CPu), and HIP. In addition, JL 13 increased 5-HT(1A) and decreased 5-HT(2A) receptors in MPC and dorsolateral frontal cortex (DFC), an effect shared by atypical antipsychotics, and may contribute to their psychopharmacological properties. Clozapine and JL 13, but not other antipsychotics, spared D(2) receptors in CPu, which may reflect their ability to induce minimal extrapyramidal side effects. In addition, JL 13 but not other typical and atypical antipsychotic drugs increased abundance of D(1) receptors in CPu and NAc. JL 13 as well as other antipsychotic agents did not alter levels of forebrain D(3) receptors. An atypical-like profile of JL 13 on DA and 5-HT receptor subtypes should encourage further development of this compound as a novel atypical antipsychotic drug.
Moran-Gates
Taylor
T
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts 02478, USA.
Massari
Carla
C
Graulich
Amaury
A
Liégeois
Jean-François
JF
Tarazi
Frank I
FI
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010077:Oxazepines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013995:Time; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C441720:5-(4-methylpiperazin-1-yl)-8-chloropyrido(2,3-b)(1,5)benzoxazepine fumarate; D014150:Antipsychotic Agents; D010077:Oxazepines; D010879:Piperazines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A; D050638:Receptors, Dopamine D4; D012701:Serotonin; D003024:Clozapine; D004298:Dopamine