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Genet Test Mol Biomarkers ; 14(3): 377-83, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20373848

RESUMEN

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.


Asunto(s)
Benzodiazepinas/síntesis química , Benzodiazepinas/farmacología , Proliferación Celular/efectos de los fármacos , Análisis Citogenético , Linfocitos/efectos de los fármacos , Intercambio de Cromátides Hermanas/efectos de los fármacos , Adulto , Alprazolam/síntesis química , Alprazolam/química , Alprazolam/farmacología , Benzodiazepinas/química , Células Cultivadas , Diazepam/síntesis química , Diazepam/química , Diazepam/farmacología , Humanos , Lorazepam/síntesis química , Lorazepam/química , Lorazepam/farmacología , Linfocitos/citología , Índice Mitótico
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