Recent advances in cholinergic drugs for Alzheimer's disease.
characterized by loss of cholinergic neurons in regions of the brain that are known to be involved in learning and memory. Cholinergic therapy seeks to compensate for this loss by pharmacological enhancement of cholinergic transmission. The use of acetylcholinesterase inhibitors, M2 antagonists, nicotinic agonists and M1 agonists has been under investigation for more than a decade. Only the acetylcholinesterase inhibitors have yielded compounds in wide clinical use, although efficacy has been modest and all suffer from dose limiting side effects. No M1 agonists or nicotinic agonists have been approved, but efforts to discover more selective compounds are continuing. Selective M2 antagonists which enhance cognition in animal models have recently been described and may provide a safer and more effective treatment for AD.
Clader
J W
JW
Cardiovascular and CNS Medicinal Chemistry Department, Schering-Plough Research Institute, Kenilworth, NJ 07033-1300, USA. john.clader@spcorp.com