Muscarinic M(1) agonists in the treatment of Alzheimer's disease.
The treatment of Alzheimer's disease attempts to correct cholinergic deficiency in the brain. In addition to the established, but restricted, efficacy of acetylcholinesterase inhibitors, attempts are being made to develop agents which will stimulate muscarinic receptors directly. This approach is logical and was found efficacious in several animal models of the disease; however none of these agents succeeded in clinical studies. Several reasons might account for this failure, which are discussed, as well as the prospects for the future.
Korczyn
A D
AD
Sieratzki Chair of Neurology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel. neuro13@post.tau.ac.il
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D000109:Acetylcholine