Aporphines. 15. Action of aporphine alkaloids on dopaminergic mechanisms in rat brain.

Of eleven aporphine analogues tested on striatal adenylate cyclase only (-)-apomorphine and (+/-)-N-n-propyl-norapomorphine (+/-(NPA)) were effective in stimulating the cyclase from rat brain. Inactive compounds included (+/-)-isoapomorphine, (-)-1,2-dihydroxyaporphine and (+/-)-10-hydroxy-N-n-propylnoraporphine. (+)-Bulbocapnine was an effective antagonist of the stimulating effects of dopamine or (-)-apomorphine on striatal adenylate cyclase. Injection of (-)-apomorphine into the lateral ventricle of rats with unilateral 6-hydroxydopamine-induced lesions of the nigro-striatal pathway caused the animals to rotate away from the side of the lesion. Intraventricular injection of 25 mug (+/-)-10-hydroxy-N-n-propylnorapomorphine was ineffective in producing rotation. The results are discussed in relation to the structural requirements for CNS dopamine receptor agonists.