抄録
Anti-anginal vasodilator trimetazidine and it's derivatives [n2-TMZ 2HCL, N-2-hydroxyethoxyethyl-N' - (2",3",4"-trimethoxybenzyl) -piperazine dihydrochloride; n2-DMZ 2HCL, N-2hydroxyethoxyethyl-N"- (3",4"- dimethoxybenzyl) -piperazine dihydrochloride] were comparatively studied with special reference to the inhibitory effects on Ca2+ mobilization of guinea pig thoracic aorta (in vitro), rabbit coronary vessel (in vivo) and human platelets (in vitro), and the following results were obtained.
1) Pre-treatment with trimetaz idine (3×10-4M), procaine (3×10-4M) and n2-TMZ (10-3M)inhibited Ca- and noradrenaline-induced contractions, but failed to affect PGF2α-in duced contractions in the guinea pig thoracic aorta.
2) ST-T wave changes on the ECG induce d by an intravenous administration of vasopressin were inhibited within 10 minutes after an intravenous administration of 15 to 20 mg/kg of trimetazidine and/or 20 to 40 mg/kg of n2-TMZ in the rabbits.
3) Trimetazidine (3×10-3M) strongly inhibited the primary human platelet agglutination induced by ADP, while n2-TMZ (3×10-4M) strongly inhibited the secondary a gglutination induced by arachidonic acid.
4) Trimetazidine (3×10M ), procaine (3×10-4M) and n2-TMZ (10-3M) had little effect on the basic activity of Ca2+ ( Mg2+) - ATPase in microsomes from the guinea pig tho r acic aorta, but completely inhibited the enzyme activity stimulated by nitroso-compo und, SIN-1A (1.0 mM).
These results suggest that the primary pharmacologic action of trimetazidine and n2-TMZ on blood vessel occurs because of an affinity to the smooth muscle cell membrane and the membrane stabilization through an inhibitory effect on Ca2+ mobilization. In this regard, the action of these drugs may be similar to that of procaine.
