Selective full dopamine D1-like (SKF-82958) and D2-like (N-0923) agonist combination in the MPTP monkey model of hemiparkinsonism.

Both SKF-82958 and N-0923, selective full D1-like and D2-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 (10 micrograms/kg) and increasing doses of SKF-82958 (23.4-234 micrograms/kg) in combination were synergistic or antagonistic in this animal model. A small dose (23.4 micrograms/kg) of SKF-82958, in combination with N-0923, caused potentiation, an intermediate dose (74.8 micrograms/kg) in combination produced additive effects, while a very large dose (234 micrograms/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 D1-like and D2-like agonists should be studied as potential therapeutic agents alone and in combination in human idiopathic parkinsonism, especially using low and intermediate doses.