The preclinical antipsychotic evaluation of HRP 913, a novel benzisoxazole derivative

✍ Scribed by Dr. Stuart Fielding; William J. Novick Jr.; Harry M. Geyer; Wayne W. Petko; Jeffrey C. Wilker; Larry Davis; Joseph T. Klein; Michael Cornfeldt

• Book ID: 102816399
• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: English
• Weight: 704 KB
• Volume: 3
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/ddr.430030305

✦ Synopsis

HRP 91 3 { I -[3-(6-fluoro-l,2-benzisoxazole-3-yI)propyl]-4-(2-oxo-l -benzimidazolinyl)} piperidine demonstrated preclinical antipsychotic activity with features that may provide a clinical advantage over current therapy. It was effective in blocking amphetamine stereotypy in rats (EDso = 0.4 mgikg, i.p.), amphetamine circling in SN-lesioned rats (EDs0 = 0.3 mgi kg, i.p.), apomorphine stereotypy in rats (ED50 = 0.8 mgikg, i.p.), but not apomorphine circling in SN-lesioned rats (up to 10 mg/kg, i.p.). It also blocked Sidrnan avoidance in rats (ED50 = 0.17 mgikg, i.p.) and monkeys (ED50 = 0.2 mgikg, p.0.) and blocked intracranial self-stimulation in rats (0.09 mg/kg, i.p.). A unique biphasic effect on catalepsy was found.

Monkey EPS studies demonstrate a potential for EPS that is lower than some existing clinical standards. HRP 913 displaced 3H-spiroperidol from rat striatal sites (ICS0 = 6.0 x lo-' M) and inhibited WB-4101 binding (Go = 2.6 x lo4 M) with only slight effect on QNB binding. HRP 91 3 does not appear to have marked u-blocking properties in vivo. HRP 91 3 is a potent dopamine antagonist and is predicted to have less side effects than current therapy.