Acute benzodiazepine administration induces changes in homocysteine metabolism in young healthy volunteers
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2009-08-31
Autores
Pompeia, Sabine 
Grego, Bruno H. C.
Pradella-Hallinan, Marcia
Hachul, Helena
Tufik, Sergio
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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. (C) 2009 Elsevier Inc. All rights reserved.
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Progress in Neuro-psychopharmacology & Biological Psychiatry. Oxford: Pergamon-Elsevier B.V., v. 33, n. 6, p. 933-938, 2009.