In vitro Studies of the Effect of Buflomedil on Platelet Responsiveness

Abstract

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 μM. 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 α₂-adrenergic antagonistic properties.

Role of catecholamines in platelet function: pathophysiological and clinical significance

“…-Adrenoceptor antagonists (phentolamine, yohimbine and idazoxan) inhibit the in vitro platelet responses to catecholamines (first and second aggregating waves, 5-hydroxytryptamine release, TXA 2 production, potentiation of the effects of other stimuli) [343][344][345]; the same action was observed in vivo following infusion of these drugs [166,177,179,202,344]. Other substances with specific pharmacological activity and -adrenoceptor blocking action, such as verapamil, ketanserine, amiloride, buflomedil and nicergoline, modulate the in vitro platelet response to catecholamines [177,[346][347][348][349][350].…”

Acceleration of wound healing by topical drug delivery via liposomes

“…The underlying mechanisms of these findings have to be considered as a complex of interlocked pharmacological effects. Buflomedil hydrochloride has been shown to induce vasodilation by competitive inhibition of α1and α2adrenoreceptors [41], to ameliorate red blood cell deformability [42] and to reduce platelet aggregation [43]. Furthermore, buflomedil increases the intracellular cAMP levels and the extracellular concentration of adenosine [44,45], which prevents activation of leukocytes and their interaction with the endothelial lining [46].…”

“…1). Consequently, the time for complete wound clo- 43 of liposome-bound agents can improve therapeutic effectiveness by extended time of local action in higher concentrations and can reduce the risk of systemic side effects [16]. To date, liposomes as a transdermal drugdelivery system have been mainly used for the application of antibiotics, steroids, or anesthetics [17,18,19,20,21].…”

Safety profile assessment of buflomedil: an overview of adverse reactions between 1975 and 2011

“…Buflomedil is an alpha-1 and alpha-2 adrenolytic agent that increases the peripheral and cerebral blood flow in impaired vascular beds, particularly at the microcirculatory level (pre-arterioles), by inducing vasodilatation, without affecting the systemic blood pressure. 1 Buflomedil inhibits platelet activation and aggregation induced by adenosine diphosphate and collagen [2][3][4] and improves elasticity of red cell membrane. 5,6 As a result of these vasoactive and haemorheological properties, buflomedil is thought to improve the blood flow in the microcirculation as well as tissue oxygenation.…”