1. Striatally-mediated response of some structurally rigid analogues of dopamine.
- Author
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Antonian L, Joseph JA, Meyerson LR, Coupet J, Schuster DI, Katerinopoulos HE, Narula AP, and Rauh CE
- Subjects
- Adenylyl Cyclases metabolism, Animals, Corpus Striatum enzymology, Dopamine pharmacology, Hydroxydopamines pharmacology, Male, Oxidopamine, Rats, Rats, Inbred Strains, Spiperone pharmacology, Stereotyped Behavior drug effects, Corpus Striatum physiology, Dopamine analogs & derivatives
- Abstract
The potency of structurally rigid analogues of dopamine (DA) at striatal dopamine receptors was evaluated in rats using three types of assessments: (a) effectiveness in producing rotational and sniffing behaviors by intrastriatal injections (b) inhibition of [3H]-spiroperidol binding and (c) stimulation of adenylate cyclase activity. The compounds included apomorphine (APO) and its analogues, (R)-2,10,11-trihydroxyaporphine (R-THA) and (R)-2-hydroxy-10,11-methylenedioxyaporphine (MDO-APO), 2-amino-6,7-dihydroxyaminotetraline (ADTN) and its analogue, exo-2-amino-6,7-dihydroxybenzonorbornene (exo-amine). (R)-THA produced no stereotypy yet it was a potent inhibitor of [3H]-spiroperidol binding and adenylate cyclase activity. MDO-APO was quite active in inducing stereotypy and stimulating cyclase activity, but it showed low potency in displacing [3H]-spiroperidol. The exo-amine and ADTN were equally potent in enhancing rotation and sniffing intensity, however, the former was completely inactive in biochemical assessments. Except for (R)-THA, all DA analogues studied elicited dopaminomimetic behavioral activities of circling and sniffing. Relationships between the actions of these drugs in the behavioral and biochemical assessments are discussed.
- Published
- 1986
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