Stereoselectivity of the interaction of muscarinic antagonists with their receptors.
The stereoselectivity of the interaction with muscarinic receptors of enantiomers of a series of chiral antagonists is receptor subtype dependent. There is no overall relationship between stereoselectivity and receptor affinity. Depending on the antagonist studied, receptor stereoselectivity may indeed reflect: (1) the weakening or loss of a single interaction involving one of the four groups bound to the asymmetric carbon; (2) steric hindrance preventing optimum interaction of the low affinity steroisomer with the receptor; and/or (3) the inversion of the relative positions of two moieties of the ligand with similar structural and electronic properties i.e. comparable affinities for the two corresponding subsites in the receptor.
Waelbroeck
M
M
Tastenoy
M
M
Camus
J
J
Feifel
R
R
Mutschler
E
E
Strohmann
C
C
Tacke
R
R
Lambrecht
G
G
Christophe
J
J
D000818:Animals; D006801:Humans; D010276:Parasympatholytics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013237:Stereoisomerism
D010276:Parasympatholytics; D011976:Receptors, Muscarinic