Cytogenetic activity of newly synthesized 1,5-benzodiazepines in normal human lymphocyte cultures

Genet Test Mol Biomarkers. 2010 Jun;14(3):377-83. doi: 10.1089/gtmb.2009.0204.

Abstract

Introduction: Many different types of benzodiazepine medications exist to treat a wide array of psychological and physical diseases based on dosage and implications. Benzodiazepines are generally considered as safe and effective drugs in short term; however, cognitive impairments and paradoxical effects occasionally occur. Our recent studies have shown that some 1,4-benzodiazepines exhibit cytogenetic activity (alprazolam, diazepam, and lorazepam) in normal human lymphocyte cultures. 1,5-Benzodiazepine derivatives are used in the synthesis of fused ring compounds, to study the chemical structure-pharmacological activity correlation. We synthesized four compounds of this category with small structural differences.

Aim: The aim of this study was to investigate their cytogenetic activity in vitro at doses equivalent to the per os doses of the used 1,4-benzodiazepines. Sister chromatid exchanges (SCEs), proliferation rate index, and mitotic index were evaluated in lymphocytes of peripheral blood cultures from two healthy donors.

Results: Three of the newly synthesized compounds exhibited positive cytogenetic activity (statistically significant reduction of SCEs, p < 0.01, t-test), without showing cytostatic properties.

Conclusion: The observed reduction of the lymphocytes' SCEs because of 1,5-benzodiazepines' activity is remarkable and requires further investigation to improve pharmacological effects.

MeSH terms

  • Adult
  • Alprazolam / chemical synthesis
  • Alprazolam / chemistry
  • Alprazolam / pharmacology
  • Benzodiazepines / chemical synthesis*
  • Benzodiazepines / chemistry
  • Benzodiazepines / pharmacology*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Cytogenetic Analysis*
  • Diazepam / chemical synthesis
  • Diazepam / chemistry
  • Diazepam / pharmacology
  • Humans
  • Lorazepam / chemical synthesis
  • Lorazepam / chemistry
  • Lorazepam / pharmacology
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Mitotic Index
  • Sister Chromatid Exchange / drug effects*

Substances

  • Benzodiazepines
  • Lorazepam
  • Diazepam
  • Alprazolam