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)‐(7‐)‐‐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.