The analgesic potential of compounds acting at acetylcholine receptors.
Compounds acting at both nicotinic and muscarinic acetylcholine receptors appear to have antinociceptive activity, and acetylcholine release in the spinal cord may be involved in endogenous pain control. The therapeutic potential of most cholinergic agonists or of agents that increase synaptic acetylcholine is limited by side effect liabilities. Recent studies, however, have identified some compounds with improved safety profiles. Multiple subtypes of nicotinic and muscarinic receptors exist, and molecular and pharmacological studies are just beginning to identify which subtypes are involved in the antinociceptive effects of cholinergic receptor activation. Further advances in this area will be necessary to determine if the rational design of subtype selective cholinergic agonists will provide novel analgesic agents.
Decker
M W
MW
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064-6125, USA. michael.w.decker@abbott.com