<I>Iso</I>nicotinic acid hydrazideの代謝並びに藥理學的作用に關する研究

Abstract

Investigating the metabolism of isonicotinic acid hydrazide (INAH) in vivo, the author obtained the following results : 1) In the urine of the rabbit, to which INAH was administered, INAH, INAH-glucose hydrazine (INAH-G) and acetyl. INAH (INAH-Ac) were detected. 2) A new method of quantitative determination of INAH with dinitrofluorobenzene was devised. With this method, free INAH and bound INAH were measured quantitatively. Unstable bound type and stable bound type were measured separately for the bound INAH. 3) The elimination rate of INAH, INAH pyruvate (INAH-pA), INAH-G and INAH-Ac in urine was about 30-70% of administered dose. The elimination rate of free INAH ws ob-served to decrease in the following order : INAH, INAH-pA, and INAH-G administered group. With the INAH-Ac administered group only stable bound type was observed. 4) The pre-treatment with pyruvic acid or glucose did not affect the total elimination rate of INAH and the elimination of bound type. 5) Pyruvic acid and glucose in the blood were observed to increase with the injection of INAH. 6) LD50 of INAH was 190 mg/kg, that of INAH-pA 5560 mg/kg and those of INAH-G and INAH-Ac were 10 g/kg and 20 g/kg respectively for mice with subcutaneous injection. 7) INAH was observed to have dilatating effect on the auricular vessel of rabbit and inhibitoryone on the movement of the isolated intestine of rabbit and the isolated uterus of rat. However with the other 3 bound types, no appreciable effects were observed. 8) Spasm was observed after some latent period with the intravenous injection of INAH in rabbit and the rabbit died with 250 mg/kg. Moderate action was observed with 836 mg/kg of INAH (equivalent to 500 mg/kg INAH), but the rabbit did not die. No action was observed either with 1220 mg/kg of INAH-G or with 652 mg/ kg of INAH-Ac (each equivalent to 500 mg/kg INAH respectively). 9) Pre-treatment with pyruvic acid or glucose did not influence the toxic effect of INAH. 10) With tests in vitro, INAH-pA was observed to have a similar degree of inhibitory action as INAH on the growth of tubercle bacillus. The action of INAH-Ac was weaker. 11) The degree of in vivo action of INAH-pA, INAH-G and INAH-Ac was observed to parallel the degree of liberation of INAH to a considerable extent.