TY - JOUR T1 - PHARMACODYNAMIC INTERACTIONS AMONG GLUCOMINERALO- AND GLUCOMINERALOCORTICOIDS, PREGNENOLONE-16α-CARBONITRILE AND VARIOUS DRUGS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 45 LP - 54 VL - 188 IS - 1 AU - Sandor Szabo AU - Panagiotis Kourounaris AU - Hans Selye AU - Ovid Da Silva Y1 - 1974/01/01 UR - http://jpet.aspetjournals.org/content/188/1/45.abstract N2 - Female rats were pretreated with corticosterone, desoxycorticosterone (DOC) acetate, fluorocortisol acetate, triamcinolone or pregnenolone-16α-carbonitrile (PCN) to determine whether they could be protected against picrotoxin, nikethamide, succinylcholine Cl, strychnine HCl, ethylmorphine HCl, acetanilide, aniline HCl, N-methylaniline, methyprylon, barbital, cyclobarbital, hexobarbital, phenobarbital, zoxazolamine, mephenesin, carisoprodol, pancuronium Br, allopurinol, sodium aurothiomalate and N-carbamoylarsanilic acid. It was found that corticosterone and DOC counteracted the effects of a few of these drugs (e.g., methyprylon, zoxazolamine, mephenesin, allopurinol). The synthetic corticoids, fluorocortisol and triamcinolone, diminished the toxicity of most of them except that of nikethamide, acetanilide, hexobarbital and carisoprodol. Triamcinolone did not protect against picrotoxin, succinylcholine and ethylmorphine, nor did fluorocortisol against cyclobarbital. PCN was ineffective only against aniline HCl, N-methylaniline, barbital, phenobarbital, sodium aurothiomalate and N-carbamoylarsanilic acid; it aggravated succinylcholine poisoning. Prophylaxis by steroids is dose-dependent. Generally, zoxazolamine paralysis was significantly diminished at the 0.1 mg dose level, maximal protection being obtained with 10 mg. Triamcinolone reduced paralysis time without lowering the blood levels of zoxazolamine (syntoxic mechanism) whereas PCN restored the righting reflex probably by decreasing the plasma concentrations of the drug (catatoxic mechanism). Fluorocortisol protected through both mechanisms. The effect of glucomineralocorticoids upon drug toxicity is closely related to glucocorticoid potency (as judged by liver-glycogen deposition and thymus involution), but mineralocorticoid activity (assessed by sodium and potassium excretion in the urine) does not seem to interfere with the influence of corticoids upon drug responses. © 1974 by The Williams & Wilkins Company ER -