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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1998-12-17
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pubmed:abstractText |
Racemic oxybutynin (CAS 1508-65-2) is used clinically to treat urinary incontinence and reportedly undergoes N-deethylation to metabolites R- and/or S-desethyloxybutynin. To assess the role of these metabolites in the therapeutic effects of oxybutynin, the antimuscarinic and antispasmodic effects of RS-, R- and S-oxybutynin, RS-, R- and S-desethyloxybutynin and, for comparative purposes, RS-terodiline (CAS 7082-21-5) on isolated strips of guinea pig bladder, were examined. All of these compounds exhibited antimuscarinic activity: they competitively antagonized carbachol-induced contractions, with mean pA2 values (+/- S.E.) of 8.91 +/- 0.20, 8.80 +/- 0.27, 7.09 +/- 0.13, 8.55 +/- 0.32, 9.04 +/- 0.32, 7.31 +/- 0.35 and 6.77 +/- 0.22, respectively. Consistent with an antispasmodic action, all of the compounds produced similar inhibition of potassium-induced contraction; the mean IC50 values for reducing responses to 137.7 mmol/l potassium were between 2.22 and 5.68 mumol/l. Thus, RS- and R-oxybutynin and RS- and R-desethyloxybutynin exhibited high antimuscarinic activity relative to their antispasmodic activity, while S-oxybutynin, S-desethyloxybutynin and RS-terodiline exhibited relatively weak antimuscarinic activity. It is concluded that deethylation of oxybutynin to desethyloxybutynin does not appreciably alter its antimuscarinic or antispasmodic activity and that R- and/or S-desethyloxybutynin probably contribute significantly to the pharmacological properties of oxybutynin in humans. In addition, since the relative potency of the antimuscarinic-to-antispasmodic actions of S-oxybutynin was equivalent to that of RS-terodiline, S-oxybutynin deserves consideration for development as a single-enantiomer drug for the treatment of urinary incontinence. It may produce the same beneficial therapeutic effects as both RS-terodiline and RS-oxybutynin but, like RS-terodiline, produce a lower incidence of antimuscarinic side-effects than seen with RS-oxybutynin.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Butylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Carbachol,
http://linkedlifedata.com/resource/pubmed/chemical/Mandelic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Parasympatholytics,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/desethyloxybutynin,
http://linkedlifedata.com/resource/pubmed/chemical/oxybutynin,
http://linkedlifedata.com/resource/pubmed/chemical/terodiline
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0004-4172
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1012-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9825119-Animals,
pubmed-meshheading:9825119-Butylamines,
pubmed-meshheading:9825119-Carbachol,
pubmed-meshheading:9825119-Guinea Pigs,
pubmed-meshheading:9825119-Isometric Contraction,
pubmed-meshheading:9825119-Male,
pubmed-meshheading:9825119-Mandelic Acids,
pubmed-meshheading:9825119-Muscle, Smooth,
pubmed-meshheading:9825119-Parasympatholytics,
pubmed-meshheading:9825119-Potassium,
pubmed-meshheading:9825119-Stereoisomerism,
pubmed-meshheading:9825119-Structure-Activity Relationship,
pubmed-meshheading:9825119-Urinary Bladder
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pubmed:year |
1998
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pubmed:articleTitle |
Comparison of the antimuscarinic and antispasmodic actions of racemic oxybutynin and desethyloxybutynin and their enantiomers with those of racemic terodiline.
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pubmed:affiliation |
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro
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