Effects of SIB-1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys.

The potential antiparkinsonian effects of the centrally acting, subtype-selective neuronal nicotinic acetylcholine receptor agonist (S)-(-)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)-pyridine (SIB-1508Y) was assessed on motor symptoms and disability scale ratings in three monkeys previously made parkinsonian by chronic exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with levodopa (L-dopa), SIB-1508Y exerted only mild antiparkinsonian effects when administered alone. Emetic effects of this drug interfered with potential therapeutic effects at higher doses. However, when a low, ineffective dose of SIB-1508Y was combined with low, ineffective doses of L-dopa, a significant clinical effect was observed. These data suggest that subtype-selective nicotinic acetylcholine receptor agonists may hold promise as antiparkinsonian agents, and when administered in combination with L-dopa may allow a reduction in the dose of L-dopa needed to achieve a significant clinical effect.