Pharmacological and Behavioral Effects of D1 Dopamine Antagonists
This work includes the effects of SCH 23390 and related benzazepines on behavior and attempts to relate these effects to their D1 dopamine antagonist action. Effects on conditioned avoidance responding (CAR) in rats were studied under the same conditions in which in vivo binding of the radioiodinated D1 specific benzazepine 125I-SCH 38840 was measured. It was found that there is very close agreement between the time-course for antagonism of CAR and for in vivo displacement of 125 I-SCH 38840 from rat striatum. The effect of SCH 23390 in CAR in monkeys was compared with standard anti-psychotics and although its oral potency was reasonable, its duration was very short (1–2 hours at 5 times its minimal effective dose for statistically significant reduction of avoidance). It is concluded from this and prior work that SCH 23390 and other D1 specific benzazepines inhibit CAR at the same doses that bind to D1 receptors in the CNS and that D1 specific antagonists are behaviorally effective at doses that do not produce D2 receptor effects (e. g. increased plasma prolactin levels catalepsy).
KeywordsDopamine Receptor Squirrel Monkey Dopamine Antagonist Charles River Breeding Laboratory Dopamine Receptor Antagonism
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- 1.Barnett, A., 1986, Review on dopamine receptors, Drugs of the Future 11: 49.Google Scholar
- 2.Barnett, A., lorio, L.C., and Billard, W., 1986, Relationship of the behavioral effects of SCH 23390 and related benzazepines to their effects on dopamine1 (D1) receptors, in: Neuromodulation of Central and Peripheral Neurotransmitter Function, Biggio G., Spano P.J., Toffano G. and Gessa G.L. eds., Fidia Research Series, Padua, Italy.Google Scholar
- 3.Cook, L. and Davidson, A.B., 1978, Behavioral Pharmacology: Animal models involving aversive control of behavior, in: Psychopharmacology A Generation of Progress, M.A. Lipton, A. Dimascio and K. Killam eds., Raven Press, New York.Google Scholar
- 5.lorio, L.C., Barnett, A., Billard, W. and Gold, E.H., 1986, Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects, in: Neurobiology of Central D-1 Dopamine Receptors, Breese G.R. and Creese I. eds., Advances in Experimental Medicine and Biology vol. 204, Plenum Press, New York.Google Scholar
- 6.lorio, L.C., Barnett, A., Leitz, F.H., Houser, V.P. and Korduba, C.A., 1983, SCH 23390, a potential benzazepine anti-psychotic with unique interactions on dopaminergic systems. J. Pharmacol. Exp. Ther., 226: 462.Google Scholar
- 7.McQuade, R., Chipkin, R., Amlaiky, N., Caron, M., lorio, L. and Barnett, A., 1988, Characterization of the radioiodinated analogue of SCH 23390; the ideal ligand for in vivo D1 dopamine receptor binding studies. Submitted to Life Sciences.Google Scholar
- 9.Tondo, L., Conway, P.G., and Brunswick, D.J., 1985, Labeling in vivo of beta adrenergic receptors in the central nervous system of the rat after administration of [ 125 I] iodopindolol, J. Pharmacol. Exp. Ther. 235: 1.Google Scholar