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 agonists, respectively, given IM produced contraversive circling and reduced neurologic deficits in six MPTP-induced hemiparkinsonian monkeys. A small fixed dose of N-0923 (1O mu g/kg) and increasing doses of SKF-82958 (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 combination 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 studied as potential therapeutic agents alone and in combination in human idiopathic parkinsonism, especially using low and intermediate doses. (C) 1997 Elsevier Science Inc.