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Pharmacologic Actions of Temiverine (p‐l NN) and its Active Metabolite, RCC‐36, on Isolated Human Urinary Bladder Muscle
Author(s) -
Kikukawa Hiroaki,
Yoshiday Masaki,
Wada Yoshihiro,
Nishi Kazuhiko,
Ueda Shoichi
Publication year - 1998
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.1998.tb00602.x
Subject(s) - oxybutynin , atropine , anticholinergic , medicine , muscarinic acetylcholine receptor , stimulation , acetylcholine , pharmacology , metabolite , active metabolite , anticholinergic agents , calcium , endocrinology , chemistry , overactive bladder , receptor , alternative medicine , pathology
Background: Temiverine (p‐INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC‐36, on isolated human bladder. Methods: Effects of temiverine and RCC‐36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCI), calcium chloride (CaCl 2 ), and electric field stimulation were evaluated using the muscle‐bath technique, and compared with the effects of atropine and oxybutynin. Results: Atropine (10 ‐9 to10 ‐6 mol/L), oxybutynin (1O ‐8 to 10 ‐5 mol/L), temiverine (10 ‐8 to 10 ‐5 mol/L), and RCC‐36 (10 ‐8 to 3 times 10 ‐6 mol/L) caused a parallel shift to the right of the concentration‐response curves to acetylcholine stimulation. The rank order of PA 2 , value was atropine > oxybutynin = RCC‐36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this atthe higher concentrations. Each drug caused a concentrationdependent inhibition of KCI (80 mmol/L)‐, and CaCl 2 , (5 mmol/L)‐induced contractile responses. Rank order of maximum inhibition was RCC‐36 = temiverine > oxybutynin > atropine. Each drug caused a concentration‐dependent inhibition of electric field‐induced contraction with or without 10 ‐6 mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC‐36 were significantly greater than that of oxybutynin. Conclusion: Atropine, oxybutynin, temiverine, and RCC‐36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC‐36 have significant inhibitory actions toward the atropine‐resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.