Interactions of benzodiazepines on psychomotor skills

Interactions of centrally active drugs are difficult to analyse in man due to methodological and ethical problems. Alcoholic and methylxanthine beverages are the most common centrally active agents that might modify the effects of benzodiazepines on performance. In sufficiently large doses ethanol enhances the effects of benzodiazepines, even those that are not metabolized by mixed function oxidases sensitive to blockade by ethanol. Consequently, the combined effect of ethanol and benzodiazepines may occur at the receptor level and/or result from altered binding of benzodiazepines to plasma proteins. Newer benzodiazepines may differ from the older in their interactions. Caffeine and theophylline counteract benzodiazepine effects on performance, resulting perhaps from the blockade of adenosine receptors which could be linked with the GABA-benzodiazepine receptor system. Central stimulants of the amphetamine type also counteract benzodiazepine effects in a somewhat selective way. New stimulant antidepressants rather counteract than increase benzodiazepine effects. Central antimuscarinics in combination with benzodiazepines are detrimental for memory. Specific benzodiazepine antagonists are effective also in man but without known clinical applications.