Pharmacology of [ 3H]apomorphine binding to bovine brain tissue

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Activity against high-affinity (nM), and over 80 per cent dopamine (DA)-agonist-displaceable binding of [ 3H]apomorphine (APO) to a “subsynaptosomal” membrane fraction of bovine caudate nucleus was evaluated using amino-6,7-dihydroxytetralin (ADTN) as a blank. Aporphines with 10,11-catechol and small N-alkyl groups were potent inhibitors ( IC 50 < 25 nM ) with parallel inhibition curves ( n h = 0.8 to 1.0). For phenethylamines, catechol and amine moieties were important structural requirements; α or β substitution markedly reduced potency. Thus, epinephrine and isoproterenol were weak while DA and its N-methylated congeners were potent; (− )norepinephrine (NE) and fluoro-DAs were intermediate in potency and ( + )NE, other catechols and hydroxylated phenethylamines were virtually inactive; m-tyramine, while weak, was more active than p-tyramine. Other DA agonists [ADTN > lergotrile > N- n-propyl-3-(3-hydroxyphenyl)-piperidine (3- PPP) > bromocriptine] were active. Neuroleptics competed relatively weakly, with imperfect correspondence to in vivo activities. Stereoselectivity was found with several aporphines, phenethylamines, and antipsychotic drugs. Many other neuropharmacologically active agents, including inhibitors of amine uptake and adrenergic receptors, were inactive. These characteristics strongly suggest that APO interacts with a DA agonist binding site in mammalian brain tissue.