Ten healthy volunteers were injected i.v. with 5 mg Ro 15-1788, a specific benzodiazepine antagonist, or placebo in a double-blind randomised design. In the EEG, Ro 15-1788 led--with some topographical variations--to a diminution of theta and alpha power, an increase of alpha mean frequency and a decrease of delta mean frequency. In auditory evoked potentials, the N1P2 and P2N2 amplitudes decreased. The electrophysiological changes induced by Ro 15-1788 are consistent with a central stimulant action. Ro 15-1788 induced some slight behavioural and subjective changes.

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The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 × 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.

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