The effects of racemic bethanechol and its (R)- and (S)-enantiomers on pre- and postjunctional muscarine receptors in the guinea-pig ileum.
The effect of racemic bethanechol and its (R)- and (S)-enantiomers on smooth muscle contraction and outflow of [3H]-acetylcholine were studied in the guinea-pig myenteric plexus-longitudinal muscle preparation that had been preincubated with [3H]-choline. (S)-, racemic, and (R)-bethanechol caused concentration-dependent contractions of the longitudinal muscle. The potency ratio of the strong isomer (S) to the weak one (R) was 915. Racemic and (S)-bethanechol concentration-dependently inhibited the evoked outflow of [3H]-acetylcholine. Racemic bethanechol was more potent than (S)-bethanechol. (R)-bethanechol up to a concentration of 1 mM did no affect the evoked outflow of [3H]-acetylcholine. (S)-bethanechol was a substrate, and (R)-bethanechol a weak inhibitor of the tissue cholinesterases. The weak cholinesterase-inhibiting action of the (R)-enantiomer probably reinforces the prejunctional effects of the (S)-enantiomer in the racemic mixture.
Schwörer
H
H
Lambrecht
G
G
Mutschler
E
E
Kilbinger
H
H
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013237:Stereoisomerism
D001626:Bethanechol Compounds; D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D018723:Bethanechol