title: Fesoterodine, its active metabolite, and tolterodine bind selectively to muscarinic receptors in human bladder mucosa and detrusor muscle.
abstract: OBJECTIVE
  To comparatively characterize the binding activity of fesoterodine, its active metabolite (5-hydroxymethyl tolterodine [5-HMT]), and tolterodine in the human bladder mucosa, detrusor muscle, and parotid gland.
  
  
  METHODS
  Muscarinic receptors in the homogenates of human bladder mucosa, detrusor muscle, and parotid gland were measured by a radioligand binding assay using [N-methyl-(3)H] scopolamine methyl chloride.
  
  
  RESULTS
  Fesoterodine, 5-HMT, and tolterodine competed with [N-methyl-(3)H] scopolamine methyl chloride for binding sites in the bladder mucosa, detrusor muscle, and parotid gland in a concentration-dependent manner. The affinity for muscarinic receptors of these agents was significantly greater in the bladder than in the parotid gland, suggesting pharmacologic selectivity for the bladder over the parotid gland. The bladder selectivity was larger for fesoterodine and 5-HMT than for tolterodine. Fesoterodine, 5-HMT, and tolterodine resulted in significantly increased (two- to five-fold) values of the apparent dissociation constant for specific [N-methyl-(3)H] scopolamine methyl chloride binding in the detrusor muscle and parotid gland, with little effect on the corresponding values of the maximal number of binding sites. This finding indicates that these agents bind to the human muscarinic receptors in a competitive and reversible manner.
  
  
  CONCLUSIONS
  Fesoterodine and 5-HMT bind to the muscarinic receptors with greater affinity in the human bladder mucosa and detrusor muscle than in the parotid gland in a competitive and reversible manner.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fuchihata
authors.forename: Shiori
authors.initials: S
authors.lastname: Kuraoka
authors.forename: Ayaka
authors.initials: A
authors.lastname: Osano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
authors.forename: Isao
authors.initials: I
authors.lastname: Araki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000378:metabolism*; D003408:Cresols / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism; D010306:Parotid Gland / Q000378:metabolism; D010665:Phenylpropanolamine / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: C109909:5-hydroxymethyl tolterodine; D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C526675:fesoterodine