Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum.
The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.
Kimoto
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Y
Division of Urology, Stanford University School of Medicine, California 94305.
Kessler
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R
Constantinou
C E
CE
D002118:Calcium / Q000378:metabolism; D004158:Diphenylacetic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D013457:Sulfur Compounds; D013737:Testis / Q000187:drug effects*
D004158:Diphenylacetic Acids; D010276:Parasympatholytics; D013457:Sulfur Compounds; D010208:Papaverine; C009488:thiphenamil; D002118:Calcium