Drotaverine interacts with the L-type Ca(2+) channel in pregnant rat uterine membranes.
The effect of the isoquinoline derivative, drotaverine on the specific binding of [(3)H]nitrendipine and [(3)H]diltiazem to pregnant rat uterine membranes was examined. Drotaverine inhibited the specific [(3)H]nitrendipine and [(3)H]diltiazem bindings with IC(50) values of 5.6 and 2.6 microM, respectively. Saturation studies showed that diltiazem caused a significant increase in the maximum binding density without changing the K(D) of [(3)H]nitrendipine while drotaverine increased both the K(D) and the B(max) of [3H]nitrendipine. The dissociation kinetics of both [3H]nitrendipine and [(3)H]diltiazem were accelerated by drotaverine. These results suggest that drotaverine has a negative allosteric interaction with the binding sites for 1,4-dihydropyridines and 1,5-benzothiazepines on the L-type Ca(2+) channel in pregnant rat uterine membranes, which may have implications as to the potential usefulness of this drug in aiding child delivery.
Tömösközi
Zsuzsanna
Z
Internal Medicine Department, Sanofi-Synthelabo CHINOIN, Tó utca 1-5, Budapest, H-1045 Hungary. zsuzsanna.tomoskozi@sanofi-synthelabo.com
Finance
Olivier
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Arányi
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004110:Diltiazem / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009568:Nitrendipine / Q000378:metabolism / Q000494:pharmacology; D010208:Papaverine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010276:Parasympatholytics; D010726:Phosphodiesterase Inhibitors; C005317:drotaverin; D009568:Nitrendipine; D010208:Papaverine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004110:Diltiazem