The Pharmacological Basis of Therapeutics
- B. N. Halpern, C. Drudi-Baracco, D. Bessirard
It is evident from the literature that there is a relation between thyroid hormones and the toxicity of drugs and other chemical substances. The administration of thyroxine or desiccated thyroid to various animal species is reported to increase susceptibility to the toxic effects of the following compounds: alloxan (Houssay and Sara, 1945), endotoxin (Kroneberg and Potzsch, 1952), cocaine, o-dinitrophenol, and dinitro-o-cresol (Glaubach and Pick, 1931, 1934), morphine (Hunt and Seidell, 1910), adrenaline (Kroneberg and Hilter, 1951), ephedrine (Halpern, Drudi-Baracco, and Bessirard, 1964), amphetamine (Moore, 1965), a non-hydrazide monoamine oxidase inhibitor (Carrier and Buday, 1961), and imipramine (Prange and Lipton, 1962). There is less evidence concerning the toxicity of drugs in the hypothyroid state; a search of the literature showed references to only two substances. The toxicity of imipramine was reported to be lower in mice in which thyroid function had been reduced by treatment with propylthiouracil (Prange, Lipton, and Love, 1963), though this was not confirmed by later studies (Prange, Lipton, and Love, 1964), and the toxicity of alloxan was reduced in thyroidectomized rats (Houssay and Sara, 1945). The purpose of this paper is to report on the toxicity of several widely used antidepressant and tranquillizer drugs in mice made hyperthyroid by the addition of desiccated thyroid to the diet, and to draw attention to possible hazards in their use in the hyperthyroid state in man. otherwise stated. The injection volume was 0.2 ml./20 g. and the animals were observed at intervals for a period of 24 hours.