The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers.
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Reitz AB, Gupta SK, Huang Y, Parker MH, Ryan RR
The preparation and human muscarinic receptor profiling of oxybutynin and N-desethyloxybutynin enantiomers.
Med Chem. 2007 Nov;3(6):543-5.
- PubMed ID
- 18045203 [ View in PubMed]
- Abstract
Oxybutynin (1) is a non-selective muscarinic receptor antagonist that is used clinically for the treatment of urinary incontinence. The major metabolite of oxybutynin in humans is desethyloxybutynin (2). We have prepared the enantiomers of 1 and 2 and evaluated their ability to displace N-CT(3)-scopolamine chloride ((3)H-NMS) binding on human cloned muscarinic m1-5 receptors. Compounds 1 and 2 potently displaced (3)H-NMS binding at m1, m3 and m4 receptors, but were less potent at the m2 and m5 subtypes. However, metabolite 2 was more potent than the parent compound 1 in the binding assay. In general the R enantiomers were more potent than their respective S enantiomers. Therefore, we suggest that the cholinergic side effects associated with 2 may be due to its greater apparent potency with m1 and m3 receptors, especially of its R-enantiomer, when compared with parent drug 1.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Scopolamine Muscarinic acetylcholine receptor M3 Protein Humans YesAntagonistDetails Scopolamine Muscarinic acetylcholine receptor M4 Protein Humans YesAntagonistDetails Scopolamine Muscarinic acetylcholine receptor M5 Protein Humans YesAntagonistDetails