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

Mov Disord. 1998 Jul;13(4):637-42. doi: 10.1002/mds.870130405.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Levodopa / pharmacokinetics
  • Macaca fascicularis
  • Male
  • Motor Skills / drug effects*
  • Neurologic Examination / drug effects
  • Nicotinic Agonists / pharmacology*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / physiopathology*
  • Pyridines / pharmacology*
  • Pyrrolidines / pharmacology*
  • Receptors, Cholinergic / physiology*
  • Receptors, Nicotinic / physiology*

Substances

  • Antiparkinson Agents
  • Nicotinic Agonists
  • Pyridines
  • Pyrrolidines
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • altinicline maleate