title: Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.
authors: Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA. william.greenlee@spcorp.com
authors: W
authors: W
authors: Greenlee
authors: J
authors: J
authors: Clader
authors: T
authors: T
authors: Asberom
authors: S
authors: S
authors: McCombie
authors: J
authors: J
authors: Ford
authors: H
authors: H
authors: Guzik
authors: J
authors: J
authors: Kozlowski
authors: S
authors: S
authors: Li
authors: C
authors: C
authors: Liu
authors: D
authors: D
authors: Lowe
authors: S
authors: S
authors: Vice
authors: H
authors: H
authors: Zhao
authors: G
authors: G
authors: Zhou
authors: W
authors: W
authors: Billard
authors: H
authors: H
authors: Binch
authors: R
authors: R
authors: Crosby
authors: R
authors: R
authors: Duffy
authors: J
authors: J
authors: Lachowicz
authors: V
authors: V
authors: Coffin
authors: R
authors: R
authors: Watkins
authors: V
authors: V
authors: Ruperto
authors: C
authors: C
authors: Strader
authors: L
authors: L
authors: Taylor
authors: K
authors: K
authors: Cox
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D006801:Humans; D018721:Muscarinic Agonists / Q000737:chemistry / Q000627:therapeutic use*; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists