Benzazepines: Structure-Activity Relationships Between D1 Receptor Blockade and Selected Pharmacological Effects
SCH 23390 is (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1-H-3-benzazepine. Its synthesis was based on the benzazepine series synthesized more than 15 years ago by Dr. Lewis Walter and Mr. Wei Chang at Schering Research Laboratories, and highlighted by the work done with the 7,8-dimethoxy analog of SCH 23390, SCH 12679. This earlier-described drug (Barnett et al., 1974) manifested potent inhibition of aggression invoked in animals by such diverse methods as social isolation, septal and olfactory bulb lesions and electrical stimulation, and aggression occurring spontaneously in monkeys (attack phenomena) and rats (muricide). With respect to antipsychotic potential, SCH 12679 did differ from the standards in that it did not block conditioned avoidance responding (CAR) in rats, an effect which we consider an important index of antipsychotic potential.
KeywordsAdenylate Cyclase Chronic Schizophrenic Wire Mesh Screen Spiperone Binding Nitrogen Lone Electron Pair
Unable to display preview. Download preview PDF.
- Albert, J.M., Elie, R., Cooper, S.F., Clermont, A. and Langlois, Y., 1977, Efficacy of SCH 12679 in the management of aggressive mental retardates, Curr. Therap. Res., 21:786.Google Scholar
- Hyttel, J., 1978, Effects of neuroleptics on 3H-haloperidol and 3H-flupentixol binding and on adenylate cyclase activity in vitro, Life Sciences, 1978, 23:551.Google Scholar
- Hyttel, J., 1983, SCH 23390-the first selective dopamine D1 antagonist, Europ J. Pharmacol, 91:153.Google Scholar
- Iorio, L.C, Hoser, V., Korduba, C.A., Leitz, F. and Barnett, A., 1981, SCH 23390, a benzazepine with atypical effects on dopaminergic systems, Pharmacologist, 23:137.Google Scholar
- Iorio, L.C., Barnett, A., Leitz, F., Houser, V.P. and Korduba, C.A., 1983, SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems, J. Pharmacol. Exp. Therap., 226:462.Google Scholar
- Itil, J.M., Stock, M.J., Duffy, A.D., Esquenazi, A., Saletu B. and Han, T.H., 1972, Therapeutic trials and EEG investigations with SCH 12679 in behaviorally disturbed adolescents, Curr. Therap. Res., 14:136.Google Scholar
- Keskiner, A., Itil, J.M., Han, T.H., Saletu, B. and Hsu, W., 1971, Clinical, toxicological and electroencephalographic study with SCH 12679 in chronic schizophrenics, Curr. Therap. Res., 13:714.Google Scholar
- Park, S., Gershon, S. and Floyd, A., 1972, A clinical trial of a benzazepine (SCH 12679) in acute schizophrenic patients, Curr. Therapy. Res., 14:298.Google Scholar