Central dopamine agonist activity on the 8-alpha-amino-ergoline CU 32-085.
The effects of the 8-alpha-amino-ergoline CU 32-085 on central dopamine neuronal systems was investigated. Two h after administration of CU 32-085 a slight increase of dopamine levels was observed in the nucleus caudatus-putamen. Radioligand binding studies in vitro have shown that CU 32-085 has a low affinity for striatal dopamine receptors labeled by [3H]n-propylapomorphine or [3H]spiroperidol. However, CU 32-085 effectively displaces in vivo [3H]n-propylapomorphine and [3H]spiroperidol from their respective binding sites in the mouse striatum. Functional studies have shown that CU 32-085 elicits contralateral rotation in rats with unilateral 6-OH-dopamine induced lesions of the meso-striatal dopamine neurons, and ipsilateral rotation in rats with unilateral intrastriatal ibotenic acid lesions. CU 32-085 relieves tremor in monkeys with ventromedial tegmental lesions and produces only slight abnormal involuntary movements. The biochemical and functional studies suggest that CU 32-085 and/or its metabolite exerts central dopamine agonist activity in vivo. Studies in monkeys with ventromedial tegmental lesions suggest that CU 32-085 might be an effective antiparkinsonian agent which produces less dyskinesias than the other tested dopamine agonists.
D000818:Animals; D000978:Antiparkinson Agents; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D014202:Tremor / Q000188:drug therapy
D000978:Antiparkinson Agents; D004873:Ergolines; D011954:Receptors, Dopamine; C031649:mesulergine; D004298:Dopamine