フェノチアジン誘導体の抗不整脈作用に関する研究(第3報) : 化学構造と抗不整脈作用,副作用並びに治療効果に就いて
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Recently some observations concerning to the antiarrhythmic action of phenothiazine derivatives especially chlorpromazine are reported. The first observation of the antiarrhythmic activity of chlorpromazine was reported by Courvoisier (1953), Kawasaki has demonstrated a suppressive effect of this drug on ectopic excitation of heart muscle produced by experimental myocardial infarction and barium intoxication in dogs. In this paper the author attempts to find a relationship between antiarrhythmic potency and chemical structure of phenothiazine derivatives and to evaluate the clinical effectiveness of chlorpromazine alone or the combined therapy with procaine amide and quinidine on various types of arrhythmias. A) Screening Method The extrasystoles were evoked in adult healthy dogs each weighing about 10kg, by intravenous injection of thiopental sodium in a dose of 0.025kg and 2% barium chloride solution in a dose of 3 mg/kg respectively. These extrasystoles continued about 60 minutes. For screening of antiarrythmic activity, a drug to be tested is injected intravenously immediately after a definite provocation of experimental arrhythmia. A positive result represents a complets cessation of arrhythmia within one minute after injection of a test material. Twenty-three preparations of phenothiazine delivatives were tested by this method. B) Relationship between antiarrhythmic action and the chemical structures 1) Most potency group : 4695R.P. was the most potency one among the phenothiazine delivatives in this experiments (Table I). The minimum effective doses was 0.1mg/kg, about one tenth that of chlorpromazine. 2) Moderate potent group : Chlorpromazine, Promazine, Acepromazine, were classified in this group. Minimum effective doses were about 1mg/kg. 3) Less potent group : 7024 R. P. Trimeprazine, 4909 R. P. Chlorpromazine S oxide, . . . These pharmacons were classified in this group. Minimum effective doses were varying from 3mg/kg to 100mg/ kg. As shown in Table I, the substistution of R (10 position of phenothiazine nucleus) has a great influence on their antiarrhythmic potency. By increasing or decreasing the number of C atoms or substitution to isoaliphatic chain in dimethylamino propyl radical of R position of chlorpromazine, their potencies were significantly decreased.
- 社団法人日本循環器学会の論文
- 1963-06-20
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