Flunitrazepam

Prevalence and clinical correlates of flunitrazepam-related complex sleep behaviors.[Pubmed:27778423]

Psychiatry Clin Neurosci. 2017 Mar;71(3):198-203.

AIM: Complex sleep behaviors (CSB) are often associated with the use of hypnotic drugs. This study investigated the prevalence and correlates of CSB among psychiatric patients who were given Flunitrazepam. METHODS: From June 2011 to May 2012, a total of 268 psychiatric outpatients who had received Flunitrazepam for at least 3 months were enrolled. Data on occurrence of CSB, demographic characteristics, Flunitrazepam dosage and duration of use, psychiatric diagnoses, physical illnesses, and alcohol use were collected. Logistic regression analysis was used to examine the clinical correlates of CSB. RESULTS: Sixty-six participants (24.6%) reported experiencing CSB. Logistic regression analysis showed that a high dosage (>2 mg/day) of Flunitrazepam (odds ratio [OR] = 1.941, 95% confidence interval [CI] = 1.090-3.455, P = 0.024) and alcohol use (OR = 1.948, 95%CI = 1.023-3.709, P = 0.042) were significantly associated with the occurrence of CSB. Sex, age, duration of Flunitrazepam use, psychiatric diagnoses, and physical illnesses were not significantly associated with the occurrence of CSB. CONCLUSION: CSB among Flunitrazepam users should be monitored routinely, especially among those receiving a high dosage who also consume alcohol.

Behavioral pharmacology of the odor span task: Effects of flunitrazepam, ketamine, methamphetamine and methylphenidate.[Pubmed:27747877]

J Exp Anal Behav. 2016 Nov;106(3):173-194.

The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task. The present experiments explored the behavioral pharmacology of a modified version of the Odor Span Task by determining the effects of stimulant drugs methylphenidate and methamphetamine, NMDA antagonist ketamine, and positive GABAA modulator Flunitrazepam. All four drugs produced dose-dependent impairment of performances on the Odor Span Task, but for methylphenidate and methamphetamine, these occurred only at doses that had similar effects on performance of a simple odor discrimination. Generally, these disruptions were based on omission of responding at the effective doses. The effects of ketamine and Flunitrazepam were more selective in some rats. That is, some rats tested under Flunitrazepam and ketamine showed decreases in accuracy on the Odor Span Task at doses that did not affect simple discrimination performance. These selective effects indicate disruption of within-session stimulus control. Overall, these findings support the potential of the Odor Span Task as a baseline for the behavioral pharmacological analysis of remembering.

The Effect of Flunitrazepam (Rohypnol((R)) ) on the Development of Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) and its Implications for Forensic Entomology.[Pubmed:27143233]

J Forensic Sci. 2016 Jul;61(4):1112-5.

This study investigated the potential effects of Flunitrazepam (known as "date rape drug") on the developmental cycle of Chrysomya megacephala, an important forensic species, and their possible implications for the calculation of the PMI. A 1050 C. megacephala eggs were divided into five groups with seven replications each. The eggs were placed on artificial diet prepared with four drug concentrations of Flunitrazepam (4, 8, 16, and 32 ng/g), besides the control group (prepared with water). Were evaluated the potential effects on development time, weight gain, and mortality during the cycles. The drug had no significant effect on development time or mortality although it did affect the weight of the pupae and adults (Kruskal-Wallis, p < 0.05). The result can be deduced that the determination of the postmortem interval is not affected.

The Importance of L-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice.[Pubmed:27957675]

Neurotox Res. 2017 Feb;31(2):309-316.

The goal of the study was to investigate the effects of drugs modifying L-arginine:NO:cGMP pathway on the development of tolerance to Flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: N (G)-nitro-L-arginine methyl ester (L-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: L-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.

Flunitrazepam rapidly reduces GABA(A) receptor subunit protein expression via a protein kinase C-dependent mechanism.[Pubmed:9723942]

Br J Pharmacol. 1998 Aug;124(7):1338-40.

Acute Flunitrazepam (1 microM) exposure for 1 h reduced GABA(A) receptor alpha1 (22+/-4%, mean+/-s.e.mean) and beta2/3 (21+/-4%) subunit protein levels in cultured rat cerebellar granule cells. This rapid decrease in subunit proteins was completely prevented by bisindolymaleimide 1 (1 microM), an inhibitor of protein kinase C, but not by N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89, 4.8 microM), an inhibitor of protein kinases A and G. These results suggest the existence of a benzodiazepine-induced mechanism to rapidly alter GABA(A) receptor protein expression, that appears to be dependent on protein kinase C activity.