The mode of actions of trimetazidine,1- (2,3,4-trimethoxybenzyl) - piperazine dihydrochloride, was pharmacologically investigated on isolated guinea-pig atria in a Locke's solution saturated with oxygen at 30°C, and the following results were obtained:
1) Trimetazidine could scarcely influence on the spontaneous contractions of atria in lower concentrations than 10
-4g/ml.
2) Trimetazidine could show an antagonistic effect against nicotine in higher concentrations than 10-5g/ml.
3) Trimetazid ine in any concentration could scarcely influence on the effect of adrenaline, acetylcholine or tyramine added in a Locke's solution.
4) The time required for the arrest of atria in a potas sium free Locke's solution was significantly prolonged in the presence of trimetazidine 10
-4g/ml. Noticable changes in potassium and sodium contents of atria induced by a potassium free Locke's solution were reduced in the presence of trimetazidine 10
-4g/ml.
5) The arrest of atrial contractions, induced by lowering the temperature of a Locke's solution from 30°C to 20°C, was prevented by trimetazidine 10
-5g/ml, which was added to the medium 15 minutes before the change of temperature.
6) Arrhythmic contractions of atria, induced by the elec trical stimulation at 3 to 5volts,5 msec. in duration and 120 cycles per minute, were fairly suppressed by trimeta zidine 10
-5g/ml which was added 15 minutes before the stimulation.
7) Trimetazidine could prolong the refractory period of atrial muscle. The effect appeared in a concentration of 10
-5g/ml in which the contractile tension of atrium was scarcely depressed by the drug.
From these experimental results, it was assumed to be clarified that trimetazidine may have effects to stabilize the atrial cell membrane and to prevent the abnormal loss of potassium ions in atria.
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