Effects of the enantiomers of 3-PPP on DA1 and DA2 dopamine receptors in the dog

The (+)- and (−)-enantiomers of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) were studied for their effects on DA₁ and DA₂ dopamine receptors in pentobarbital anesthetized dogs. 3-PPP enantiomers were administered into the renal artery after phenoxybenzamine pretreatment to determine possible DA₁ activity; dopamine was also injected for comparison. DA₂ activity was determined by injection of the enantiomers into the femoral vascular bed with intact nerve supply and without phenoxybenzamine; dipropyl dopamine (DPDA) or apomorphine were used as standard DA₂ agonists. Antagonists activity of the enantiomers on DA₁ or DA₂ receptors was determined by simultaneous administration of the enantiomer with DA in the renal vascular bed and with DPDA or apomorphine in the femoral vascular bed. Neither enantiomer was active as a DA₁ agonist, but both exhibited antagonist activity. Both enantiomers were found to be agonists of the DA₂ receptor; in addition, both showed DA₂ antagonist activity. In all actions the (−)-enantiomer was approximately 4 times more potent than the (+)-enantiomer.