Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4.

摘要: The goals of the present study were: (1) to investigate thc binding properlies oi (R)- and (S)-procyclidine two aehiral derivatives muscarinie M1• M2 M4 reeeptor subtypes (2) identify interaetions which allow these receptors diseriminate between stereoisomers. (R)-Procyclidine showed a higher affinity for human neuroblastoma NB-OK 1 M rat striatum musearinie 4 receptors. a~ compared cardiac 2 (S)-Procyclidine had 130-iold lower than (R)-procyclidine 40-fold Pyrrinol. diphenyl derivative with eyclohexyl g.roup (S}-procyclidine replaeed by phenyl group, has an eight-fold M1 as eompared (R)-procycli­ dine, three-fold Hexahydro-procyclidine. eorresponding achiral dicyclohexyl compound, 10- 20-fold three reeeptors. inerease in free energy, is observed when groups procyelidine are separately cyclohexyJ groups, respectively. was additive ease • receptcrs. This indicates that musearinic s!ereoseleetivity based on eoexistence sites, one preferring phenylrather group seeond cyclohexyl rather group. In addition. there were aiso sites hydroxy moiety protonated amino ligands. greater stereoselectivity (R)-procyelidine reflected better fit subsite Musearlnie M, reeeptors; Muscarinie Musearinic receptor~~ (S}-Procyelidine; (R)-Procyclidine; Pyrrinol; Hexahydro-procyclidine; (stereose1ecti\ity)