鎮咳薬の化学的薬理学的研究(第10報) : 1,2-Diphenyl-1-tert-aminoethane誘導体の薬理, 特に1,2-Diphenyl-1-pyrrolidinoethaneの光学異性体の作用比較

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Pharmacological activities of three optical isomers of 1,2-diphenyl-1-pyrrolidinoethane hydrochloride were examined. A) Differences in pharmacological activities of the isomers were as follows : (1) Antitussive effect : The 50% antitussive doses of the d-, dl-and l-isomers, evaluated by the "coughing dog and cat" methods, were 2.84,1.92,and 1.18 mg/kg (i.v.), respectively, in unanesthetized dogs ; 3.30,2.02 and 1.36 mg/kg (i.v.), respectively, in lightly pentobarbitalized cats. In dogs, all of the isomers tested were more potent than codeine ; the l-isomer, the most potent one, was 3.18 times, and even the least potent d-isomer was 1.25 times as effective as codeine. (2) All of the three isomers were more potent than codeine in the potentiating action on hexobarbital anesthesia in mice. The l-isomer was the most potent in this action, followed by the dl- and d-isomers. (3) In the hypothermic action on rat body temperature, the dl- and l-isomers were weaker than the d-isomer, and the l-isomer was the weakest. (4) The d-isomer produced a significant inhibitory effect on transportation of intestinal contents in mice. On the other hand, the dl- and l-isomers had no effect. (5) All the three isomers were more potent than procaine in both surface and infiltration anesthesia in guinea pigs. The l-isomer was the most potent in this action, followed by the dl- and d-isomers. The potency of the isomers ranged from 1.6 to 2.8 times that of procaine. B) The three isomers showed similar qualitative as well as quantitative effects in the following items : (1) Toxic symptoms and LD_<50> in mice. (2) No analgesic action in mice. (3) Effects on respiration and blood pressure in urethanized rabbits. (4) Antagonistic effect on acetylcholine-, BaCl_2-, and histamine-induced spasms of the isolated guinea pig ileum. C) Pharmacological characteristics of d-isomer as an antitussive were as follows : The safety margin of antitussive effect by intravenous administration in the dog was roughly estimated as 8.8-10.6,which is a smaller value than that of codeine. The antitussive effect of the compound was not antagonized by Nalorphine. However, tolerance developed rapidly by repeated daily administrations. No withdrawal symptoms were observed by an abrupt withdrawal of the compound or Nalorphine substitution.
公益社団法人日本薬学会の論文
1970-01-25

鎮咳薬の化学的薬理学的研究(第10報) : 1,2-Diphenyl-1-tert-aminoethane誘導体の薬理, 特に1,2-Diphenyl-1-pyrrolidinoethaneの光学異性体の作用比較

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