ISSN:
1442-2042
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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 (CaCl2), 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 PA2, 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 CaCl2, (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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1442-2042.1998.tb00602.x
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