Research ReportsEffects of JL13, a pyridobenzoxazepine compound, in dopaminergic and glutamatergic models of antipsychotic activityAndrade, Yane C.P.a; Ropke, Jivagoa; Viana, Thércia G.a; Fanelli, Chiaraa; Minaldi, Elisaa; Batista, Luara A.b; Issy, Ana C.c; Del Bel, Elaine A.c; Rodrigues, Lívia C.M.d; Liégeois, Jean-Françoise; Moreira, Fabrício A.aAuthor Information aDepartment of Pharmacology, Institute of Biological Sciences bDepartment of Pharmacology, Graduate School in Neuroscience, Universidade Federal de Minas Gerais, Belo Horizonte cDepartament of Morphology, Estomatology and Basic Pathology, Faculty of Odontology of Ribeirão Preto, Universidade de São Paulo Ribeirão Preto dDepartment of Physiological Sciences, Health Science Center, Universidade Federal do Espírito Santo, Vitória, Brazil eDepartment of Pharmacy, Laboratory of Medicinal Chemistry, Faculty of Medicine and CIRM, University of Liège, Liège, Belgium Received 3 February 2020 Accepted as revised 21 August 2020 Correspondence to Fabrício A. Moreira, PhD, Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, 31270-901 MG, Brazil, E-mail: [email protected] Behavioural Pharmacology: February 2021 - Volume 32 - Issue 1 - p 2-8 doi: 10.1097/FBP.0000000000000595 Buy Metrics Abstract The pyridobenzoxazepine compound, 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13), has been developed as a potential antipsychotic drug. We tested the hypothesis that JL13 is efficacious in both dopaminergic and glutamatergic animal models of schizophrenia. We investigated JL13 for its efficacy to prevent cocaine- and ketamine-induced hyperlocomotion and MK-801-induced deficits in prepulse inhibition (PPI) of the startle reflex. Male Swiss mice received injections of JL13 (0.1–10 mg/kg) and were tested in the open field for basal locomotion. In separate experiments, the animals received injections of JL13 (0.1–3 mg/kg) followed by cocaine (10 mg/kg), ketamine (60 mg/kg), or MK-801 (0.5 mg/kg) and were tested in the open field for hyperlocomotion. In addition, it was also tested if JL13 prevented MK-801-induced disruption of PPI. Only the highest dose of JL13 impaired spontaneous locomotion, suggesting its favorable profile regarding motor side effects. At doses that did not impair basal motor activity, JL13 prevented cocaine-, ketamine-, and MK-801-induced hyperlocomotion. Moreover, JL13 prevented MK-801-induced disruption of PPI. Extending previous findings, this study shows that JL13 exerts antipsychotic-like activity in both dopaminergic and glutamatergic models. This compound has a favorable pharmacological profile, similar to second-generation antipsychotics. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.