Central dopamine agonist activity on the 8-α-amino-ergoline CU 32-085

Abstract The effects of the 8-α-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 [ 3 H]n-propylapomorphine or [ 3 H]spiroperidol. However, CU 32-085 effectively displaces in vivo [ 3 H]n-propylapomorphine and [ 3 H]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.