Stereoselective inhibition of prolactin secretion by (-)-HW-165, a novel 3-PPP congener; further support for similarities between central DA autoreceptors and pituitary lactotroph DA receptors.

The novel atypical dopamine (DA) receptor agonist HW-165 (trans-7-hydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)quinoline), a 'rigid' 3-PPP congener, and its enantiomers were investigated with regard to their actions on prolactin (PRL) release in rats. Racemic HW-165 dose dependently inhibited the elevation of PRL secretion induced by monoamine synthesis disruption (NSD 1015) combined either with abolished DA nerve impulse flow (GBL) or with monoamine depletion (reserpine). Racemic HW-165 was roughly equipotent to 3-PPP but 5-10-fold less potent than apomorphine. The PRL inhibitory action of racemic HW-165 was stereoselectively prevented by the DA antagonist (+)-butaclamol. Since the chiral aspect of lactotroph DA receptor activation by 'atypical' DA receptor agonists has not been covered in previous investigations the effects of the HW-165 enantiomers were now studied. Our findings suggest that the PRL inhibitory properties of racemic HW-165 reside in its (-) enantiomer, (+)-HW-165 being devoid of activity. Taken together, the results reinforce the concept that the pituitary lactotroph DA receptors mediating the inhibition of PRL release are similar, notably also from a stereochemical point of view, to central DA receptor sites with presumed high agonist sensitivity, such as DA autoreceptors.