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  • Title: [General pharmacology of aclacinomycin A (author's transl)].
    Author: Ohmori K, Hirano S, Hori S.
    Journal: Jpn J Antibiot; 1980 Feb; 33(2):192-213. PubMed ID: 6929361.
    Abstract:
    The general pharmacology of aclacinomycin A, a new antitumor antibiotic, was studied in mice, rats, guinea-pigs, frogs, rabbits and dogs. The LD50 values of aclacinomycin A were 32.5 mg/kg (i.v.), 30.1 mg/kg (i.p.), 33.9 mg/kg (s.c.) and 69.7 mg/kg (p.o.), respectively in male mice, and 28.8 mg/kg (i.v.), 21.1 mg/kg (i.p.), 26.4 mg/kg (s.c.) and 58.6 mg/kg (p.o.), respectively in male rats. Aclacinomycin A had no effect on the central nervous system except potenciation of the pentobarbital sodium-induced anesthesia in mice. The contraction of isolated heart was stimulated in frogs while slightly inhibited in rabbits at higher concentration. Transient increases in the heart rate and the blood flow of peripheral vasculature were observed but the blood pressure was slightly lowered with respiratory excitation in anesthetized rabbits and dogs. The ECG (II-lead) demonstrated slight depression of R wave amplitude and slight sinus arrhythmia in dogs. Aclacinomycin A inhibited the contraction of isolated smooth muscle and antagonized some spasmogens. It inhibited the spontaneous movement of isolated rabbit ileum and rat uterus at higher concentration, and antagonized acetylcholine, histamine, serotonin and barium chloride in the contraction of isolated guinea-pig ileum. The antagonism was competitive to oxytocin and noncompetitive to acetylcholine in rat uterus, and noncompetitive to noradrenaline in rat deferent duct. The drug showed no apparent effect on the gastrointestinal propulsion in mice and on mucous membrane of the stomach in rats. However, it depressed gastric acid secretion in rats while slightly increased bile secretion in guinea-pigs. Urine volume and urinary excretion of electrolytes (Na+, K+) decreased in rats. Vascular permeability was slightly inhibited by the drug in rabbits and mice. No hemolytic effect was shown. Aclacinomycin A showed no antigenicity in anaphylactic reaction and SCHULTZ-DALE reaction in guinea-pigs.
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