In vitro studies of the effect of buflomedil on platelet responsiveness.
The effect of buflomedil (Fonzylane; Laboratoire Lafon, Maisons-Alfort, France) on platelet function, a drug used clinically for the treatment of peripheral vascular diseases, was investigated in vitro. The compound significantly inhibits epinephrine-induced aggregation at the micromolar level. At higher doses (approximately 1 mM), a weak inhibition of ADP- and collagen-induced aggregation was observed; at these concentrations, buflomedil inhibits granular secretion and the interaction of fibrinogen with its receptor on platelet. Further investigations indicate that the drug affects calcium uptake at the membrane level and inhibits the binding of [3H]-yohimbine to the same extent as observed with phentolamine. The IC50 determined from competition binding assays was 1 +/- 0.5 microM. This value was consistent with the affinity constant approximated for the binding of [3H]-buflomedil to non-stimulated platelets. Taken-together, these results indicate that the vasoactive compound buflomedil is a weak antiaggregating agent which exhibits alpha 2-adrenergic antagonistic properties.
Ryckewaert
J J
JJ
Unité INSERM 217, DRF/LBIO/Laboratoire d'Hématologie, Grenoble, France.
Maurel
A
A
Marguerie
G
G
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011759:Pyrrolidines; D015016:Yohimbine; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen; D002118:Calcium; C010651:buflomedil; D004837:Epinephrine