Effects of JL13, a Pyridobenzoxazepine with Potential Atypical Antipsychotic Activity, in Animal Models for Schizophrenia

ABSTRACT JL13 [5-(4-methylpiperazin-1-yl)-8-chloro-pyrido [2,3-b][1,5] benzoxazepine fumarate] is a substance with a close structural resemblance to clozapine. However, it is less sensitive to oxidation and may therefore have less hematological side effects. In the present study, JL13 was compared with clozapine and haloperidol in several animal models for schizophrenia. The paw test represents a screening model for antipsychotic drugs that can discriminate between drugs with extrapyramidal side effects and drugs without. Haloperidol increased both forelimb retraction time and hindlimb retraction time (HRT), whereas both clozapine and JL13 increased only HRT. In the prepulse inhibition paradigm, all three drugs reversed the apomorphineand the amphetamine-induced disruption of prepulse inhibition. However, whereas haloperidol was equally effective against both dopaminergic drugs, JL13 and clozapine were more effective against amphetamine. Finally, only JL13 was able to increase prepulse inhibition in normal rats, whereas only clozapine reduced basal startle amplitude. Taken together, these data suggest that JL13 may be an effective antipsychotic drug, with a profile similar to clozapine

The behavioral effects of acute and chronic JL 13, a putative antipsychotic, in Cebus non-human primates

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The effects of JL 13, a pyridobenzoxazepine with potential atypical antipsychotic activity, in animal models for schizophrenia

peer reviewe

Treatment of mild-to-moderate arterial hypertension with pinacidil alone or in combination with hydrochlorothiazide

This multicenter, open-label, uncontrolled study included 98 patients with mild-to-moderate hypertension and assessed the efficacy of pinacidil alone or in combination with hydrochlorothiazide (HCTZ) for 135 days. The initial dosage of pinacidil was 12.5 mg twice daily. The dosage was increased to 25 mg twice daily if diastolic blood pressure remained >90 mm Hg after 30 days. If blood pressure was still not controlled in 30 days, HCTZ 12.5 mg twice daily could be added. If target blood pressure was not reached after 30 days of combination therapy, the regimen was increased to pinacidil 25 mg twice daily plus HCTZ 12.5 mg twice daily. In addition, HCTZ could be added at any time if peripheral edema developed. Systolic and diastolic blood pressures decreased significantly after 30 days of treatment from 162.1 ± 14.1 mm Hg (mean ± SD) and 102.1 ± 5.0 mm Hg to 153.2 ± 14.9 mm Hg and 92.8 ± 9.0 mm Hg, respectively. Some additional benefit was observed during the following months of drug administration. Systolic and diastolic blood pressures were 140.5 ± 11.4 mm Hg and 84.3 ± 6.7 mm Hg, respectively, at the end of the study. At that time, 32 patients (32.7%) were receiving pinacidil only, 12.5 mg twice daily; 20 patients (20.4%) were receiving pinacidil 25 mg twice daily; and 46 patients (46.9%) were receiving pinacidil and HCTZ twice daily. HCTZ was added for incomplete blood pressure control in 15 patients (32.6%) and for peripheral edema in 31 patients (67.4%). The addition of HCTZ to pinacidil reduced the incidence of edema from 65.4% to 15.2%. The results of this study suggest that pinacidil was associated with a significant reduction in systolic and diastolic blood pressures in patients with mild-to-moderate hypertension. The high incidence of peripheral edema was largely reduced by the addition of HCTZ.SCOPUS: ar.jinfo:eu-repo/semantics/publishe