On the mechanism of action of amezinium methylsulphate on the dog saphenous vein.

Strips of dog saphenous vein were used to study the multiple effects of amezinium methylsulphate (AM) on adrenergic mechanisms. The ED50 of the contractile effect was 0.55 microM. After the maximal response to AM had been obtained, increasing the concentration of AM resulted in relaxation; a larger contraction occurred after washout. AM was not able to cause contraction of strips obtained from dogs pretreated with reserpine; phentolamine shifted the dose-response curve of AM to the right. AM 0.1 and 10 microM enhanced the sensitivity of the strips to noradrenaline (NA) about 3.5 and 11 times respectively. When the cocaine-like effect was excluded (by using cocaine itself, either alone or after pretreatment with reserpine) an alpha blocking effect of AM was demonstrated at a concentration of 100 to 150 microM. In homogenates from venous tissue, AM inhibited monoamine oxidase (MAO) activity. AM inhibited preferentially MAO type A, since the IC50 was 5 microM for MAO A and greater than 1 mM for MAO B. In the intact tissue, AM 0.01 microM reduced the formation of [3H]dihydroxyphenylglycol [3H ]DOPEG) without significantly altering the accumulation of [3H]NA or the formation of the other metabolites. AM 0.1 microM reduced the accumulation of NA, and AM 10 microM abolished the accumulation of [3H]NA, reduced the formation of deaminated metabolites and enhanced the formation of [3H]normetanephrine [3H ]NMN). In washout experiments of strips preloaded with [3H]NA, AM enhanced the efflux of [3H]NA and the effect began with 1 microM; washout of AM sustained the efflux of [3H]NA for at least 30 min. The deaminated metabolite [3H]DOPEG was significantly decreased.