Effects and plasma levels of N-desmethyldiazepam after oral administration in normal volunteers.

Psychopharmacologia
H H Dasberg

Abstract

In the course of a previous study on the pharmaco-kinetics and effects of diazepam in anxiety patients, it was hypothesized that the N-desmethyl derivative is a disturbing agent causing side effects. The present study served to test the validity of this assumption. Diazepam and N-desmethyl-diazepam, the latter as a separate drug, were orally administered to 6 subjects, each drug during 7 days, 15 mg daily in divided doses. Using a randomized, placebo controlled, double-blind design, subjective and observer ratings of a wide range of clinical effects were made. Plasma levels of the benzodiazepine compounds were determined by the G.L.C. method. Results showed that steady state plasma levels were reached on the 5th day; the N-desmethyldiazepam, considering its lower clearance rates, is a longer acting drug than diazepam; that both substances induce hypnosedative effects, mood changes, and somatic disturbances and facilitate sexual behaviour in normals; that desmethyldiazepam is a more effective hypnosedative and mood-lowering substance as compared to equal doses of diazepam. Further comparisons in anxiety patients are recommended in order to find out if the specific desmethyldiazepma effects are therapeutically favourable or distu...Continue Reading

References

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Citations

Jan 1, 1982·European Journal of Drug Metabolism and Pharmacokinetics·G M PacificiR Gomeni
Jan 1, 1990·Pharmacology & Therapeutics·L BertilssonJ Reviriego
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Feb 1, 1986·Journal of Pharmacokinetics and Biopharmaceutics·E A Lane, I Parashos
Mar 1, 1984·Journal of Pharmaceutical Sciences·S CotlerW A Colburn

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