STRESS MODIFICATION OF DRUG RESPONSE.

Rats stressed by unilateral hind-leg ligation show a significantly decreased pharmacological response to the effects of hexobarbital, meprobamate, and pentobarbital. This effect is dependent upon an intact pituitaryadrenal axis, since it is absent in both hypophysectomized and adrenalectomized animals. It can be simulated by intravenous administration of adrenocorticotrophic hormone or corticosterone. The effect of stress on drug response is not noted with barbital, a compound which is not metabolized; this effect is inhibited by treatment of the animal with a drug metabolism inhibitor such as SKF 525-A (diethylaminoethyl 2,2-diphenylpentanoate). Compounds which can stimulate adrenocorticotrophic hormone secretion or act directly on the adrenals to produce corticosteroids should thus be able to stimulate their own metabolism or that of other drugs.