Abstract
Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.
Highlights
Flunitrazepam (FNZ) is a potent benzodiazepine agonist primarily used as a hypnotic and preanesthetic agent across Europe (Woods, Winger, 1997; Druid, Holmgren, Ahlner, 2001)
When examining the cytotoxicity of the benzodiazepine FNZ at various concentrations (0.2, 1.0, 5.0 and 10.0 μg/mL) in vitro (Table I), the results showed that this substance did not affect cytokinesis-block proliferation and showed no cytotoxic action in hepatoma cells from R. norvegicus
The base concentration used in this study was extrapolated to the total weight of the culture medium (5 g) based on the highest concentration consumed by humans (2 mg) and concentrations up to 50 times higher than this concentration were used, the concentrations used in this study are much smaller than the 50 μg/mL concentration that was used in Assaf AbdelRahman’s (1999) work, which may explain the lack of cytotoxicity observed in the hepatoma de Rattus norvegicus (HTC) cells
Summary
Flunitrazepam (FNZ) is a potent benzodiazepine agonist primarily used as a hypnotic and preanesthetic agent across Europe (Woods, Winger, 1997; Druid, Holmgren, Ahlner, 2001). FNZ is a sedative benzodiazepine that is prescribed for the short-term treatment of insomnia at a recommended dose of 0.5-1.0 mg, with a maximum dose. Similar to other cerebral modulating drugs, FNZ can produce pharmacological effects that include sedation, memory impairment, and behavioral disinhibition, which is described as an increase in the probability of behaviors that typically occur at low frequencies due to social and. Vicentini interpersonal constraints, such as sexual misconduct. These disinhibitory and amnesic effects might result in increased risky behavior and altered decision-making (e.g., violence, other drug use and high-risk sexual activity) (Wu, Schlenger, Galvin, 2006; Lane, Cherek, Nouvion, 2008)
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