Theory and statistics of detecting synergism between two active drugs: cocaine and buprenorphine.

This article discusses the theory and statistical aspects in the design and analysis of experiments to detect synergism between two drugs that produce overtly similar effects. The current analysis extended and simplifies previously published work in this area. Application is made to a study by Kimmel et al. in this issue that examined the combined action of buprenorphine and cocaine in producing turning in rats having unilateral nigrostriatal lesions produced by 6-hydroxydopamine. The use of turning as an endpoint is unusual in quantitative studies of synergism in that no clear maximum effect (turning), could be elicited. Data from the turning study are analyzed statistically and reveal that the combination of buprenorphine and cocaine in each of two fixed ratio mixtures tested is synergistic for this effect.