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

作者：Pompeia Sabine^*; Grego Bruno H C; Pradella Hallinan Marcia; Hachul Helena; Tufik Sergio; D'Almeida Vania

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2009, 33(6): 933-938.

DOI：10.1016/j.pnpbp.2009.04.017

• Benzodiazepine
• Cortisol
• Cysteine
• Gender
• Homocysteine
• Cysteine

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 market of life-threatening disorders, the mechanisms involved in the decrease of these amino acids are potential targets for clinical application.

• 出版日期2009-8-31