Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. I. Theoretical considerations and literature review.

The considerations necessary to describe the effects of combinations of drugs in a biological system are reviewed. The terms which express these effects-additive, potentiative, antagonistic, synergistic-have not had specific operations applied to them and mathematical models have been sought to define these operations. The models should (1) describe the nature of the action of single drugs, (2) classify the results of drug combinations, (3) provide a set of operations for deciding the outcome of combinations, and (4) predict all possible results of a combination from a knowledge of each drug acting alone. Research on the effects of alcohol and meprobamate and their interactions is reviewed, including behavioral and pharmacological studies and also some studies of the interaction of alcohol with other drugs. The task of characterizing the relation between the drug and response is formidable because complex physiological and biochemical processes determine the relationship between administered and effective dose and are further complicated by route of drug administration and various time relations. The descriptions of biochemical and physiological events seem well advanced; those of behavior are not. Much of the behavioral research assumes that a single dose is representative of all doses of the drug, and that combinations of the drugs and additivity of effects can be determined without a rigorous definition or means of application. [Bibliography of 249 items.]