SELECTIVE FULL DOPAMINE D-1-LIKE (SKF-82958) AND D-2-LIKE (N-0923) AGONIST COMBINATION IN THE MPTP MONKEY MODEL OF HEMIPARKINSONISM

Both SKF-82958 and N-0923, selective full D-1-like and D-2-like agonis ts, respectively, given IM produced contraversive circling and reduced neurologic deficits in six MPTP-induced hemiparkinsonian monkeys. A s mall fixed dose of N-0923 (1O mu g/kg) and increasing doses of SKF-829 58 (23.4-234 mu g/kg) in combination were synergistic or antagonistic in this animal model. A small dose (23.4 mu g/kg) of SKF-82958, in com bination with N-0923, caused potentiation, an intermediate dose (74.8 mu g/kg) in combination produced additive effects, while a very large dose (234 mu g/kg) in combination produced antagonism. All three doses of SKF-82958 prolonged the duration of action of a small dose (10 ng/ kg) of N-0923. Selective D-1-like and D-2-like agonists should be stud ied as potential therapeutic agents alone and in combination in human idiopathic parkinsonism, especially using low and intermediate doses. (C) 1997 Elsevier Science Inc.