In vivo interaction of cabergoline with rat brain dopamine receptors labelled with [3H]N-n-propylnorapomorphine.

Cabergoline is a potent dopaminergic agent that interacts with agonists and antagonists of dopamine receptors in vitro. We studied the binding of [3H]N-n-propylnorapomorphine ([3H]NPA) to dopamine receptors after i.v. and oral administration of cabergoline to determine whether cabergoline crosses the blood-brain barrier; bromocriptine was used as a reference drug. Cabergoline and/or its active metabolite(s) did cross the blood-brain barrier and reach dopamine receptors. Comparative time-course analysis of the regional inhibition of [3H]NPA binding showed that cabergoline was more potent than bromocriptine in inhibiting [3H]NPA binding and that it occupied the receptor for longer. These effects were observed in all areas of the rat brain studied (striatum, olfactory tubercles, adeno- and neurohypophysis, thalamus and hypothalamus). Further studies in the striatum and adenohypophysis showed that cabergoline receptor occupancy was dose-dependent and still detectable 72 h after i.v. administration of the drug. While cabergoline was more potent in the striatum than in the adenohypophysis when administered i.v., the reverse was observed after its oral administration. Cabergoline was equally potent in the adenohypophysis after oral and i.v. administration, as determined 1 and 8 h later.