Spinal Effects of the Fesoterodine Metabolite 5-Hydroxymethyl Tolterodine and/or Doxazosin in Rats With or Without Partial Urethral Obstruction

dc.contributor.authorFuellhase, Claudius
dc.contributor.authorSoler, Roberto [UNIFESP]
dc.contributor.authorGratzke, Christian
dc.contributor.authorBrodsky, Marina
dc.contributor.authorChrist, George J.
dc.contributor.authorAndersson, Karl-Erik
dc.contributor.institutionWake Forest Univ
dc.contributor.institutionUniv Munich
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionPfizer Inc
dc.description.abstractPurpose: the combination of muscarinic receptor and alpha(1)-radrenoceptor antagonists is increasingly used for benign prostatic hyperplasia related lower urinary tract symptoms. in addition to the well established peripheral site of action, little is known about the central effects of muscarinic receptor antagonists and muscarinic receptor/alpha(1)-adrenoceptor antagonist combinations on bladder function, partly due to poor brain penetration after systemic administration. We assessed the effects of intrathecal 5-hydroxymethyl tolterodine, an active metabolite of fesoterodine, in obstructed and nonobstructed rats, and of combined intrathecal 5-hydroxymethyl tolterodine/doxazosin in a rat model of partial urethral obstruction.Materials and Methods: We used 80 male Sprague-Dawley (R) rats to test various doses of intrathecal 5-hydroxymethyl tolterodine and/or intrathecal doxazosin on urodynamic parameters. Urodynamic evaluation without anesthesia was done 3 days after bladder and intrathecal catheterization. Two weeks before urodynamics 40 rats underwent partial urethral obstruction.Results: Intrathecal 5-hydroxymethyl tolterodine had no urodynamic effects in nonobstructed rats. Compared to controls obstructed rats had increased bladder pressure and weight, and voiding frequency. in obstructed rats 5-hydroxymethyl tolterodine restored urodynamic parameters to those seen in nonobstructed animals. Doxazosin had effects similar to those of intrathecal 5-hydroxymethyl tolterodine. When the 2 drugs were combined, at the doses used only small additional effects were observed.Conclusions: Urodynamic changes in obstructed rats can be normalized by intrathecal 5-hydroxymethyl tolterodine and by intrathecal doxazosin. the central pathways on which the 2 drugs act seem to be up-regulated with partial urethral obstruction and less relevant under normal conditions.en
dc.description.affiliationWake Forest Univ, Wake Forest Inst Regenerat Med, Winston Salem, NC 27157 USA
dc.description.affiliationUniv Munich, Dept Urol, Univ Hosp Grosshadern, Munich, Germany
dc.description.affiliationUniversidade Federal de São Paulo, Div Urol, São Paulo, Brazil
dc.description.affiliationPfizer Inc, New York, NY USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Urol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Council of Technological and Scientific Development, Brazil
dc.identifier.citationJournal of Urology. New York: Elsevier B.V., v. 184, n. 2, p. 783-789, 2010.
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Urology
dc.rightsAcesso restrito
dc.subjectprostatic hyperplasiaen
dc.subjectadrenergic alpha-antagonistsen
dc.subjectmuscarinic antagonistsen
dc.titleSpinal Effects of the Fesoterodine Metabolite 5-Hydroxymethyl Tolterodine and/or Doxazosin in Rats With or Without Partial Urethral Obstructionen