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.
Domino
E F
EF
Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D008254:Macaca nemestrina; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C071262:SK&F 82958; C047508:rotigotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine