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

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Abstract
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.