Interactions of Steroid Hormones with Centrally Acting Drugs

Abstract

A study has been made of the effects of steroid hormones on the pharmacological activity of certain centrally-acting drugs. The Introduction contains a brief description of the known hormonal effects of steroids together with the historical background to the introduction of the synthetic steroids into clinical medicine. Some emphasis is placed on the ways in which steroids may affect central nervous sensitivity to drugs; their possible intra-cellular mechanisms of action and pathways of metabolic degradation are also discussed. The experimental part of this project has involved the pretreatment of mice or rats for a number of days with a synthetic glucocorticoid, mineralocorticoid, oestrogen or progestin. Subsequently, these animals have received some centrally-acting drugs, for example, an analgesic, sympathomimetic Stimulant , anti-convulsant or barbiturate, and their responses compared with those in animals of un-altered hormonal state. A number of techniques and pieces of apparatus have been devised, important amongst which are a method for the assay of plasma barbiturate levels and devices for measuring anti-nociceptive activity and hypnotic activity. The most marked and sustained effects were produced by pretreatment of mice with oestrogens or progestins. The effects of certain barbiturates and related agents were markedly attenuated by progestin pretreatment, whereas, in -3- direct contrast, their effects were markedly enhanced by oestrogens. A study of plasma barbiturate levels suggested that there were effects in the rates of metabolism of these drugs, and similar changes in the metabolism of morphine may also have been produced. Nevertheless, a number of other observations, for example, certain minimal changes in brain biogenic amine levels and the response of mice to centrally-acting sympathomimetics suggest that there occurred also changes in the inherent sensitivity of the central nervous systems of these animals. The mice were more sensitive to the effects of the sex steroids than they were to pretreatment with adrenocorticoids, whereas experience with rats was the reverse. Finally, the Discussion summarises the possible interactions of steroids and centrally-acting drugs in experimental animals, and concludes with a study of the possible clinical implications of combining long-term steroid treatment with the concomitant use of other drugs such as hypnotics, analgesics, anti-convulsants and stimulants. The simultaneous use of centrally-acting drugs and long-term steroids, including those taken for contraceptive purposes, should be attended by caution.