TERATOGENICITY OF CAFFEINE IN MICE RELATED TO ITS MODE OF ADMINISTRATION

In teratological experiments with drugs, the injection by ways of parenteral routes is often used for the advantage of securing certain effects, especially exact dosage-response relation. It has been presumed that the teratogenic action of a drug varies with the mode of parenteral administration, even if the same total daily dosage is employed and this may be due to the variations in the nature of metabolites of a drug and their concentration or duration in the embryonic tissues. There is little information in this area at hand. Isaacson and Chaudhry (1) reported that the incidence of cortisone-induced cleft palate in mouse embryos is higher when administration of 4 small doses at 6-hour interval is given rather than a single dose of the total amount. The teratogenicity of caffeine in mice was established and some of its mechanisms were studied by our group (2-4). The rapid metabolic rate and no apparent accumulation in the body of this compound established in man (5) can be presumably applied to other mammals. So the administration of caffeine could be an advantageous tool for analytical studies of teratogenicity in experimental mammals. This study was undertaken to establish a relationship between teratogenic activity and some modes of administration by using this compound. © 1969, The Japanese Pharmacological Society. All rights reserved.