Effect of naftidrofuryl on platelet-induced vasospasm in vitro. Role of antiserotonergic actions.
This study was designed to analyse the spasmolytic actions of naftidrofuryl (Dusodril, CAS 31329-57-4) more in detail, using isolated vessel segments of bovine coronary arteries (BCA). In this preparation, naftidrofuryl caused a dose-dependent inhibition of 5-HT, U 46.619 ((5Z, 9a, 11a, 13E, 15S)-11,9-(epoxymethano) prosta-5,13-dienoic acid), PGF2 alpha and KCl-induced contractions. Additionally, the actions of naftidrofuryl on platelet-induced vasospasm were investigated using arachidonic acid (AA)-stimulated platelets and BCA. Naftidrofuryl antagonized the vasocontractile effects of secreted 5-HT, but was only slightly active in reducing the TXA2-dependent vessel contraction. The suppression of ADP-induced platelet aggregation and secretion required more than 300 mumol/l naftidrofuryl. These data support the concept of a spasmolytic activity of naftidrofuryl which also involves the antagonism of platelet-derived vasocontractile mediators.
Verheggen
R
R
Department of Neurosurgery, University Hospital & School of Medicine, Göttingen, Fed. Rep. of Germany.
Schrör
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009257:Nafronyl / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D012702:Serotonin Antagonists; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D009257:Nafronyl; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost