Comparative studies on the effects of tolmesoxide (Rx71107), a tolmesoxide metabolite (Rx71112) and nifedipine in isolated blood vessels.

1 The effect was studied of tolmesoxide (Rx71107), a tolmesoxide metabolite (Rx71112) and nifedipine on active tension in human isolated crural veins and in rat thoracic aorta. The effects of tolmesoxide and nifedipine on (22)Na and (45)Ca net influx in noradrenaline-induced contractions were investigated in rat thoracic aorta.2 Tolmesoxide, Rx71112 and nifedipine caused a concentration-related inhibition of noradrenaline (NA)- and potassium (K(+))-induced contractions in human veins. Nifedipine was by far the most potent drug in these respects. Tolmesoxide (4.7 muM-4700 muM) and Rx71112 (22 muM-220 muM) inhibited the NA-induced contraction more effectively than the K(+)-induced concentration. The reverse was true for nifedipine (0.0023-3 muM).3 Nifedipine had a similar potency in inhibiting the NA-induced contraction in rat aorta and human veins, whereas the inhibitory effect of tolmesoxide was more pronounced in rat aorta than in human veins.4 Tolmesoxide was a weak antagonist of the contractile effects of the cumulative addition of calcium on human veins. In concentrations up to 470 muM, tolmesoxide was completely devoid of inhibitory effects on (22)Na and (45)Ca net influx in rat aorta. Rx71112 (220 muM) had an inhibitory effect on (22)Na net influx but no significant effect on (45)Ca net influx.5 Nifedipine was an effective antagonist of the contractile effects of cumulative addition of calcium in human veins and had a concentration-related inhibitory effect on both (22)Na and (45)Ca uptake in rat aorta.6 The results indicate that tolmesoxide and Rx71112 cause dilatation of human crural veins in vitro at concentrations that do not interfere with the net transmembranal movements of Ca and are thus clearly different from the effects of nifedipine.