Lachowicz_1999_Life.Sci_64(6-7)_535

Reference

Title : SCH 57790: a novel M2 receptor selective antagonist - Lachowicz_1999_Life.Sci_64(6-7)_535
Author(s) : Lachowicz JE , Lowe D , Duffy RA , Ruperto V , Taylor LA , Guzik H , Brown J , Berger JG , Tice M , McQuade R , Kozlowski J , Clader J , Strader CD , Murgolo N
Ref : Life Sciences , 64 :535 , 1999
Abstract :

As a decrease in cholinergic neurons has been observed in Alzheimer's Disease (AD), therapeutic approaches to AD include inhibition of acetylcholinesterase to increase acetylcholine levels. Evidence suggests that acetylcholine release in the CNS is modulated by negative feedback via presynaptic M2 receptors, blockade of which should provide another means of increasing acetylcholine release. Structure-activity studies of [4-(phenylsulfonyl)phenyl]methylpiperazines led to the synthesis of 4-cyclohexyl-alpha-[4-[[4-methoxyphenyl]sulfinyl]-phenyl]-1-piperazin eacetonitrile. This compound, SCH 57790, binds to cloned human M2 receptors expressed in CHO cells with an affinity of 2.78 nM; the affinity at M1 receptors is 40-fold lower. SCH 57790 is an antagonist at M2 receptors expressed in CHO cells, as the compound blocks the inhibition of adenylyl cyclase activity mediated by the muscarinic agonist oxotremorine. This compound should be useful in assessing the potential of M2 receptor blockade for enhancement of cognition.

PubMedSearch : Lachowicz_1999_Life.Sci_64(6-7)_535
PubMedID: 10069520

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Citations formats

Lachowicz JE, Lowe D, Duffy RA, Ruperto V, Taylor LA, Guzik H, Brown J, Berger JG, Tice M, McQuade R, Kozlowski J, Clader J, Strader CD, Murgolo N (1999)
SCH 57790: a novel M2 receptor selective antagonist
Life Sciences 64 :535

Lachowicz JE, Lowe D, Duffy RA, Ruperto V, Taylor LA, Guzik H, Brown J, Berger JG, Tice M, McQuade R, Kozlowski J, Clader J, Strader CD, Murgolo N (1999)
Life Sciences 64 :535