Comparative study of central dopaminergic properties of RU 29717 (N-propyl-9-oxaergoline) and pergolide.
RU 29717, a 9-oxaergoline derivative, has been compared with pergolide in a variety of biochemical and behavioural tests indicative of dopaminergic (DAergic) activity. RU 29717 and pergolide have a similar affinity for DA receptors labelled by [3H]spiroperidol or [3H]dihydroergocryptine ( [3H]DHEC) by using striatal or anterior pituitary membranes respectively. Both compounds stimulate the striatal DA-sensitive adenylate cyclase and inhibit the activity of this enzyme in dispersed cells from the neurointermediate lobe of the pituitary gland. In anterior pituitary cells in primary culture, they decrease prolactin release with the same efficacy. In vivo, they exert a long-lasting inhibition of the reserpine-induced hyperprolactinemia. They equally retard the alpha-MPT-induced disappearance of striatal DA and increase striatal acetylcholine levels. In behavioural models, the similarity between RU 29717 and pergolide is also evident: they induce contralateral circling in animals lesioned unilaterally with 6-OHDA, produce stereotyped behaviour and have emetic activity within the same dose range. Therefore, RU 29717, like pergolide, is a potent direct acting DAergic agonist. In experimental models used to investigate this activity at the striatal or the anterior pituitary levels the compounds present a similar profile of action.
D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D004285:Dogs; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D008297:Male; D010479:Pergolide; D010903:Pituitary Gland, Anterior / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D004873:Ergolines; D011954:Receptors, Dopamine; D010479:Pergolide; C037493:N-propyl-9-oxaergoline; D011388:Prolactin; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D004298:Dopamine