title: Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics.
abstract: The new flavone derivative REC 15/2053, a compound with spasmolytic activity on the lower urinary tract, was examined for its in vitro interaction with alpha- and beta-noradrenergic receptors, dopaminergic, muscarinic, serotoninergic, and opiate receptors, and calcium-channel binding sites labeled with 1,4-dihydropyridines from normal rat brain. All the investigated receptors are directly or indirectly involved in the nervous control of the lower urinary tract functions. The activity of REC 15/2053 on these receptors was studied in comparison to the most common drugs used in the management of urinary bladder disorders such as flavoxate, emepronium bromide, oxybutynin, terodiline, and imipramine. REC 15/2053 showed only weak binding to [3H]nitrendipine sites (IC50 = 14 microM) and muscarinic receptors (IC50 = 18 microM), whereas flavoxate was slightly active only at muscarinic receptors (IC50 = 12.2 microM). Emepronium bromide, oxybutynin, and terodiline were active only at muscarinic receptors, with IC50 values of 236, 5.4, and 588 nM, respectively. Oxybutynin showed a weak affinity to [3H]nitrendipine binding sites (IC50 = 44.4 microM). Imipramine was active at alpha 1-adrenergic and muscarinic receptors (IC50 = 248 and 653 nM, respectively). The activity of REC 15/2053 at muscarinic receptors and 1,4-dihydropyridine binding sites seems too low to account for its mechanism of action.
authors.affiliation: Laboratori di Ricerca, Recordati S.p.A., Milano, Italia.
authors.forename: G A
authors.initials: GA
authors.lastname: Abbiati
authors.forename: R
authors.initials: R
authors.lastname: Ceserani
authors.forename: D
authors.initials: D
authors.lastname: Nardi
authors.forename: C
authors.initials: C
authors.lastname: Pietra
authors.forename: R
authors.initials: R
authors.lastname: Testa
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry; D005419:Flavonoids / Q000378:metabolism*; D005422:Flavoxate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009568:Nitrendipine / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D010276:Parasympatholytics; D011955:Receptors, Drug; D005422:Flavoxate; D011813:Quinuclidinyl Benzilate; D009568:Nitrendipine; C059474:terflavoxate