藥物作用の温度係數に關する研究

Abstract

The time needed to produce a regular action by the various drugs (digitalis, strophanthine, strychnine, picrotoxin, guanidine, chloral hydrate and urethane) was measured at intervals of 5°C at the temperature of 10°C to 30°C or 35°C. In this case the dosage of each drug was changed at each temperture over a wide range, and thus temperature coefficient at each range of temperature was calculated. The results are as follows : (1) Between 15°C and 30°C temperature coefficient was not remarkably different in any drugs, increased in proportion to increase of dosage of drugs and its value was about 2. (2) In the experimental examples at 30°C to 35°C the value ot temperature coefficient (Q10) was fairly large in picrotoxin and strophanthine and on the contrary Q10 was small in urethane. At the low temperature of 10°C to 15°C Q15 became abruptly large but became reversely small in urethane. So the changing point seemed to be in the range of the above temperature. This changing point in strophanthine was about 13°C. (3) In the experiment which the surrounding temperature was artificially changed Q10 coincided with the above results. Therefore increase or decrease of the time needed to produce the action by the seasonal change seems chiefly to be due simply to the difference of the surrounding temperature. (4) The little difference of temperature coefficient among each drug should prove that the chemical change of drugs themselves or the direct participation of drugs to cellular metabolism must not be the essential quality of action of drugs. The reason which Van't Hoff's law can be applied to action of drugs may be thought that the rate of adsorption of drugs into the active point of cells is under the influence of temperature. (5) Temperature coefficient of action of drugs injected subcutaneously takes the genuine value near by the minimum effective dosage. When the time needed to the gradual increase of concentration in blood in proportion to the increase of dosage of drugs is permitted, temperature coefficient takes the larger value than the genuine one, and the process which drugs are absorbed into the blood vessel through the part injected subcutaneously does not give an influence to temperature coefficient, because in this case there may be not adsorption. (6) When the relation between the minimum effective dosage of each drug and temperature at 15°C aud 25°C was investigated, it was found that the minimum effective dosage hardly changed by the difference of temperature but had possibility to become slightly small at high temperature. (7) After all temperature coefficient of action of drugs is not nearly estimated from the active dosage, but is determined by the comparison of the time needed to produce the action of a certain dosage of drugs.