化學構造上メチル基及びエチル基の相違と藥理學的作用との關係について 特にN-原子に結合せる兩基の比較

Abstract

In order to determine the differences in effect of methyl and ethyl radicals in pharmacological actions, I compared compounds having one, two, or three methyl radicals with those in which the methyl radicals had been substituted with the ethyl radicals respectively and vice versa. Results : (1) For comparing the differences in effect of methyl and ethyl radicals in compounds having single methyl or ethyl radical, I have chosen meperidine hydrochloride (a), an analgesic, and a compound (b) which was obtained by substituting the methyl radical attached to nitrogen of the meperidine hydrochloride with an ethyl radical. No qualitative differences were observed. However, the action of (b) appeared to be slightly weaker than that of (a) as shown by LD50 in mice and the tests for analgesic action by the hot plate method and the respiratory depressant action in rabbit by the Wright's respiratory apparatus. (2) As an example of compounds having two methyl and ethyl radicals, the respiratory stimulants, coramine (nikethamide) (c) and cycliton (e) were compared with compounds derived from them by the substitution of the ethyl radicals by the methyl radicals respectively (d, f). Not only considerable quantitative differences were observed in LD50 in mice, minimal convulsive doses and, in respiratory stimulant action, but also qualitative differences were observed. Where as (c) and (e) had only stimulant action, (d) and (f) had depressast action in small dosage and stimulant action in large dosage. As a further example the sedatives, coumarine-3-carboxylic acid diethylamide (g) and its methyl substituted coumarine-3-carboxylic acid dimethylamide (h) were compared (h) was weaker in hypnotic action but was more toxic. Qualitative differences were also observed in the respiratory stimulant action and in the convulsive state. (3) As an example of three methyl and ethyl radicals, carbaminoyl choline chloride (i) was compared with a compound derived from it by the substitution of its three methyl radicals by three ethyl radicals (j). Althoush (i) exhibited series of actions observable when three parasympathetic nerve is stimulated. (j) had none of such actions. Also difference in LD50 in mice of (j) and (i) was very great, (j) being 200 times that of (i).