Investigation into some aspects of EMIT d.a.u., TLC, and GC-MS urinalysis of bromazepam. (1/15)

Among the different 1,4-benzodiazepine urinary metabolites, those of bromazepam possess distinctive chemical features that may be used in their selective isolation and detection. The detection of bromazepam metabolites in urine was carried out using EMIT d.a.u., thin-layer chromatography (TLC), and gas chromatography-mass spectrometry (GC-MS). The positive EMIT d.a.u. benzodiazepine assay for bromazepam was found to be due to the 3-hydroxybromazepam (3HOB) metabolite. The detection by TLC and GC-MS was carried out after enzyme or acid hydrolysis of the glucuronide conjugates. Both the 2-amino-3-hydroxy5-bromobenzoylpyridine (AHBBP) metabolite and the acid hydrolysis product of 3-HOB, 2-amino-5-bromobenzoylpyridine (ABBP), were selectively detected by TLC. The bromazepam metabolites in urine could be both isolated and detected selectively by GC-MS in the presence of the metabolites of other 1,4-benzodiazepines that were sometimes used in combination with bromazepam. Both 3-HOB and AHBBP were detected by GC-MS only after trimethylsilyl (TMS) derivatization and not as the free compounds or the acetyl derivatives. Only ABBP was detected in three forms: ABBP, the TMS derivative, and the acetyl derivative. Evidence has been obtained from the enzyme hydrolysis and the TLC studies for the formation of the glucuronide conjugate of AHBBP at the 3-OH group rather than at the 2-NH2 group. All the results have been validated using reference 3-HOB and AHBBP.  (+info)

Hair to document drug-facilitated crimes: four cases involving bromazepam. (2/15)

The use of a drug to modify a person's behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, so-called DFSA, robbery) has caused alarm in the general public. Drugs used can be difficult to detect (active products at low dosages, chemical instability), possess amnesic properties, and can be quickly cleared from body fluids. In case of long delay between the alleged crime and clinical examination, collection of blood or even urine can be of little value. This is the reason why this laboratory developed an original approach based on hair testing by liquid chromatography-tandem mass spectrometry. To explore the detectability of a single absorption of bromazepam in hair, two volunteers (male and female) received a 6-mg dose. A strand of hair was sampled about one month after exposure and was cut into three segments of 2-cm long. After pulverization, 20 mg of hair was incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was extracted with 5 mL of a mixture of diethyl ether/methylene chloride (80:20) in the presence of diazepam-d5, which was used as internal standard (IS). Hair extract was separated on a XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 316.0 to 182.2 and 209.3 and m/z 290.1 to 154.1 and 198.2 for bromazepam and the IS, respectively. In the hair of the two subjects, bromazepam was detected in the proximal segment at 0.8 and 4.7 pg/mg, respectively. Hair analysis was applied to four authentic criminal cases. In the two first cases, bromazepam tested positive in the corresponding hair segment at 5.7, and 10.3 pg/mg. In another case, head hair was sampled 19 weeks after the alleged offense, and its length (< 4 cm) did not allow analysis of the corresponding period. However, 4.1 pg/mg of bromazepam was quantified in the victim's pubic hair. In these three cases, concentrations were consistent with a single exposure to bromazepam. In the last case, bromazepam was detected at 15 pg/mg in the segment corresponding to the period of the alleged offence but also in the range 2 to 7 pg/mg in the four other consecutive segments, making a single exposure statement difficult.  (+info)

[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study]. (3/15)

The P300 component of the event-related potential (ERP) is a general measurement of "cognitive efficiency". It is an index of the ability of an individual's central nervous system (CNS) to process incoming information. OBJECTIVE: To compare the neuromodulatory effects of caffeine and bromazepam on the visual ERP (P300), in relation to a P300 normative database. METHOD: 15 right-handed individuals (7 male and 8 female), between 20 and 30 years of age, healthy, free of any cognitive impairment and not making use of psychoactive substances were studied. Participants were submitted to a visual discrimination task, which employed the "oddball" paradigm, after the administration of caffeine and bromazepam, in a randomized, double-blind design. RESULTS: Statistically significant differences were observed when the caffeine and bromazepam conditions were compared to the normative database. CONCLUSION: The present results suggest that caffeine and bromazepam have distinct modulatory effects on CNS functioning.  (+info)

Analysis of the influence of bromazepam on cognitive performance through the visual evoked potential (P300). (4/15)

Benzodiazepines have been used in the pharmacological treatment of anxiety for over four decades. However, very few studies have combined bromazepam and event-related potentials (ERP). The present study aimed at investigating the modulatory effects of this drug on brain dynamics. Specifically, the effects of bromazepam (3 mg) on the P300 component of the ERP were tested in a double-blind experiment. The sample, consisting of 15 healthy subjects (7 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Electrophysiological (P300) and behavioral measures (stroop, digit span, and reaction time) were analyzed across three experimental conditions: placebo 1, placebo 2, and bromazepam. Results suggest that the effects of bromazepam (3 mg) on cognitive processes are not apparent. In spite of what seems irrefutable in current literature, bromazepam did not produce evident effects on the behavioral and electrophysiological variables analyzed.  (+info)

Comparison of behavioral effects after single and repeated administrations of four benzodiazepines in three mice behavioral models. (5/15)

The behavioral and clinical profiles of various benzodiazepines after acute and chronic treatment are not well defined and may differ. The aim of this study was to evaluate the behavioral profiles of alprazolam, bromazepam, diazepam and lorazepam in mice after single and repeated (every half-life for seven half-lives) administrations using a stimulation-sedation test (actimeter), a myorelaxation test (rotarod), and an anxiolysis test ("four plates"). A dose range from 0.03 to 4 mg/kg was used. A single administration of alprazolam showed stimulating and anxiolytic effects which diminished after repeated administration. Lorezapam's sedative effect diminished but its anxiolytic effect increased upon repeated administration. Except for lorazepam, the myorelaxing effect of all four drugs increased after repeated treatment. These results suggest that the behavioral profile of benzodiazepines may not be identical during acute and chronic treatment. These differences may be present in clinical treatment and warrant investigation in humans.  (+info)

Influence of bromazepam on cortical interhemispheric coherence. (6/15)

Benzodiazepines are among the most commonly prescribed medications due to their therapeutic efficacy in reducing anxiety and inducing sleep. Consequently, they have been widely employed in the pharmacological treatment of several disorders. Nevertheless, few studies have analyzed the effects of bromazepam in electroencephalographic activity (EEG). The present study aimed at investigating the modulatory effects of this drug on brain dynamics. Specifically, the effects of bromazepam (3mg) on EEG coherence were tested in a double-blind experiment. The sample, consisting of 10 healthy subjects (5 male and 5 female), was submitted to ten minutes of EEG recording. The electrophysiological measure (coherence) was analyzed across three experimental conditions: bromazepam, placebo 1, and placebo 2. Results indicate that bromazepam significantly increases cortical interhemispheric coherence.  (+info)

The effects of bromazepam on the early stage of visual information processing (P100). (7/15)

The early stages of visual information processing, involving the detection and perception of simple visual stimuli, have been demonstrated to be sensitive to psychotropic agents. The present study investigated the effects of an acute dose of bromazepam (3 mg), compared with placebo, on the P100 component of the visual evoked potential and reaction time. The sample, consisting of 14 healthy subjects (6 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs the initial stage of visual information processing, as observed by an increase in P100 latency.  (+info)

Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam. (8/15)

1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid-brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid-brain region of rats subjected to benzodiazepine treatment.2 Chronic therapy with either of the two anti-anxiety agents enhanced the endogenous levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons-medulla, mid-brain and striatum.3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid-brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5-hydroxy-indoleacetic acid levels is not associated with enhanced deamination of 5-hydroxytryptamine.4 Discontinuation of treatment for 48 h significantly decreased the activity of mid-brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine-treated and normal rats. The concentrations of mid-brain tryptophan and 5-hydroxytryptamine were also reduced in various brain regions examined.5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5-hydroxyindoleacetic acid.6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5-hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.  (+info)

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