Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.
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 (KCl), 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) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 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 at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (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.


CONCLUSIONS
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.
Kikukawa
H
H
Department of Urology, Kumamoto University School of Medicine, Japan.
Yoshida
M
M
Wada
Y
Y
Nishi
K
K
Ueda
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010648:Phenylacetates / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010648:Phenylacetates; C107100:RCC 36; D011189:Potassium Chloride; D001285:Atropine; C105354:temiverine; C005419:oxybutynin; D002122:Calcium Chloride; D000109:Acetylcholine