Behavioral effects and dopamine antagonist properties of N-alkylaminobenzazepines

✍ Scribed by J.B. Acri; J.H. Shah; A.H. Newman; Y.P. Belov; A.S. Basile; L.G. Sharpe; J.M. Witkin

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 815 KB
• Volume: 37
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199601)37:1<39::aid-ddr2>3.0.co;2-n

✦ Synopsis

Blockade of dopamine D, receptors has been suggested as a novel therapeutic approach to psychotic disorders and to psychomotor stimulant dependencies. Peripheral D, receptors have also been implicated in the acute lethal effects of cocaine. Attempts to synthesize a D, antagonist that does not penetrate the central nervous system led to the discovery of novel series of N-alkylammobenzazepine D, antagonists. In the present study, the most potent compound of that series, JHS 271, suppressed locomotor activity, and blocked cocaine-stimulated activity, apornorphine-induced stereotypies, and the lethal effects of cocaine in mice. Structural analogs of JHS 271 were also evaluated in selected assays. Potencies in these tests demonstrated a significant positive correlation with affinities for the D, receptor. These results implicate D, receptor blockade as a mechanism of action for JHS 271 and related compounds. Comparative studies of central vs. systemic administration and determination of blood/brain concentrations indicdted that JHS 271, like SCH 23390, can readily access central sites upon systemic application. o