三環系薬物の生体膜におよぼす影響
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Effects of tricyclic drugs, imspramine (IM), desipramine (DMI), chlorimipramine (CIM) and chlorpromazine (CPZ) on isolated rat hepatocytes, crude mitochondrial fraction and erythrocytes were studied at various concentrations. Loss of intracellular enzyme into surrounding media was used to quantitate cytotoxic effects. Inhibition of hypotonic hemolysis of rat erythrocytes was measured as hemoglobin concentration.<BR>The potency of leakage of total GOT (t-GOT) and mitochondrial GOT (m-GOT) was CPZ>CIM>DMI>IM. All drugs caused decrease in GPT leakage at 1 × 10<SUP>-4</SUP>M but CPZ and CIM caused increase in GPT leakage at 4 × 10<SUP>-4</SUP>M. The potency of leakage of LDH was CPZ>CIM>DMI>IM. All drugs caused decrease in enzyme leakage with decreasing incubation temperature. The potency of leakage of β-glucuronidase from crude mitochondrial fraction was CPZ>CIM>DMI>IM.<BR>The ability of various drugs to inhibit the hypotonic hemolysis is considered to represent a membrane stabilizing effects. Maximum inhibition of the hypotonic hemolysis was observed at a concentration of 1 × 10<SUP>-4</SUP>M in CPZ and CIM, and 4 × 10<SUP>-4</SUP>M in DMI and IM. The concentration of drugs causing enzyme leakage from hepatocytes were coincided with the concentration causing hemolysis. The rank order of surface activity was the same as that of hepatotoxicity and hemolysis in vitro. These results suggest that the differences in membrane damage produced by tricyclic drugs may be related to surface activity which in turn may determine the extent of adsoption onto cell membranes.
- 学校法人 昭和大学・昭和医学会の論文
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- 三環系薬物の生体膜におよぼす影響