A PHYSICOCHEMICAL MODEL FOR MECHANISM OF ACTION OF ANTIHISTAMINICS AND CORTISOL

The mechanism of action of antihistaminies and cortisol has been studied at the molecular level using “coupled” ion-exchange membrane electrodes on an in vitro system consisting of bovine serum albumin as the receptor and various antihistaminies and cortisol as competitors. The data obtained indicate that, when the antihistaminie concentration is above a critical value (1 × 10-1 M), histamine does not induce those changes in bovine serum albumin which are necessary for an interaction. At the same time, structural analogs without antihistaminie activities have shown no influence on the binding of histamine, when tested in the same experimental conditions. Furthermore, the access of histamine to the biopolymer is inhibited by molar concentrations of antihistaminies which closely approximate those previously found for inorganic monovalent ions. The correlation between ionic strength and antihistaminie action is discussed in terms of a stabilizing effect of the antihistaminie on a given conformation of the biopolymer. This conformation is unable to bind histamine. When antihistaminies are replaced by cortisol, this steroid prevents the binding of histamine to the macroion at molarities at which antihistaminics show no effect. In fact, under the same experimental conditions, cortisol is more effective by a factor of 10 than antihistaminies in stabilizing that cordon histamine. © 1969, American Chemical Society. All rights reserved.