Acute benzodiazepine administration induces changes in homocysteine metabolism in young healthy volunteers

Prog Neuropsychopharmacol Biol Psychiatry. 2009 Aug 31;33(6):933-8. doi: 10.1016/j.pnpbp.2009.04.017. Epub 2009 May 3.

Abstract

Purpose: High cortisol plasma concentrations have been shown to be associated with increases in homocysteine levels. Here we studied whether decreases in cortisol concentration, induced by an acute oral dose of a benzodiazepine, could decrease homocysteine, and if changes were similar in both genders.

Methods: This was a double-blind, cross-over design study of acute oral flunitrazepam (1.2 mg) and placebo in young, healthy, male and female (n=21) volunteers. Blood samples were collected 3 h after ingestion (after peak-plasma concentration of flunitrazepam was reached). Various biochemical parameters were analysed, such as plasma homocysteine, cysteine, folate, vitamins B6, B12, and sexual hormones.

Results: Flunitrazepam reduced cortisol (p=0.0011), cysteine (p=0.014) and homocysteine (p=0.028) concentrations, irrespective of gender. No correlations were found between cortisol and other biochemical markers (all r's<0.03). Concentration of cysteine and homocysteine were negatively correlated with plasma flunitrazepam concentration, suggesting that changes in these amino acids might be related to the metabolism of this benzodiazepine.

Conclusion: Acute administration of flunitrazepam decreases plasma homocysteine and cysteine by mechanisms that seem unrelated to changes in cortisol. Given the importance of homocysteine as a marker of life-threatening disorders, the mechanisms involved in the decrease of these amino acids are potential targets for clinical application.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Benzodiazepines / administration & dosage*
  • Cross-Over Studies
  • Cysteine / blood
  • Cysteine / metabolism
  • Double-Blind Method
  • Female
  • Homocysteine / blood
  • Homocysteine / metabolism*
  • Humans
  • Male
  • Young Adult

Substances

  • Homocysteine
  • Benzodiazepines
  • Cysteine