Disease relevance of Quazepamum

• All 20 reported daytime somnolence (drowsiness, lethargy, or sleepiness), and one quazepam-treated patient also had hypokinesia [1].
• Eleven patients, six receiving quazepam and five receiving the placebo, had adverse experiences, including ataxia, which was observed in two quazepam-treated and one place-bo-treated patient [2].
• 7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster [3].

Psychiatry related information on Quazepamum

• Withdrawal of triazolam was associated with sleep and mood disturbances (rebound insomnia and rebound anxiety), whereas quazepam exerted carryover effectiveness [4].
• On the other hand, SJW, but not quazepam impaired psychomotor performance in the DSST test [5].
• Nocturnal traffic noise, sleep, and quality of awakening: neurophysiologic, psychometric, and receptor activity changes after quazepam [6].
• Quazepam had the least sedative effect of the 3 drugs tested, showed a time lag at the onset of its effects and a more prolonged effect on psychomotor impairment than reported previously [7].
• At various time points after either quazepam or flurazepam administration, pharmacological activity was measured by the inhibition of electroconvulsive shock (ECS)-induced seizures [8].

High impact information on Quazepamum

• Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam [4].
• The kinetics of quazepam and 2-oxoquazepam can be best described by a two-compartment open model with first-order absorption/formation kinetics [9].
• Maximum concentration and AUC of quazepam and 2-oxoquazepam and AUC of N-desalkyl-2-oxoquazepam were somewhat higher after nighttime dosing, most likely a result of decreased apparent volume of distribution of the central compartment after the nighttime dose (5.0 l/kg for nighttime dosing and 8.6 l/kg for morning dosing) [10].
• Triazolam, zolpidem, quazepam, and placebo were administered orally in a double-blind, crossover design [11].
• Binding of [3H]GABA was studied in frozen-thawed and repeatedly washed cortical membranes incubated in 20 mM KH2PO4 plus 50 mM KCl, pH 7.4, at 4 degrees C in the absence and presence of quazepam or its metabolites [12].

Chemical compound and disease context of Quazepamum

• To evaluate the efficacy and safety of reduced doses of the benzodiazepine agonist quazepam in older insomniacs, 30 men and women > 60 years old with chronic insomnia were randomly assigned to receive 0, 7.5, or 15 mg quazepam [13].

Biological context of Quazepamum

• Multiple-dose quazepam kinetics [9].
• The high affinity central benzodiazepine binding sites can be differentiated into BZ1 and BZ2 receptors by ligands (such as triazolopyridazines and Quazepam) that preferentially act on BZ1 sites [14].
• Effect of dietary fat content in meals on pharmacokinetics of quazepam [15].
• These findings show that food intake has an evident effect on quazepam absorption, but further studies are needed to clarify a determinant factor of this alteration (2.5-fold for Cmax and 2.1-fold for AUC(0-8), on average) [15].
• Drug interaction between St John's Wort and quazepam [5].

Anatomical context of Quazepamum

• These results suggest that quazepam may act through facilitation of the EEG-synchronizing mechanisms localized in the lower brain stem which are involved in physiological EEG-synchronizing and sleep-inducing processes [16].
• Excretion of quazepam into human breast milk [17].
• It was found that quazepam and two of its metabolites have a higher affinity for benzodiazepine receptors in cerebellum than for those in hippocampus, indicating a preferential interaction of these compounds with BZ1-receptors [18].
• Diazepam, quazepam and the beta-carboline, ZK 93423, enhanced the specific binding of [3H]GABA in a concentration-dependent manner (10(-7)-10(-5) M) in the cerebral cortex and hippocampus but not in the spinal cord and cerebellum [19].
• Itraconazole inhibited the formation of OQ from quazepam, HOQ from OQ and DOQ from OQ in human liver microsomes with Ki values of 8.40, 0.08 and 0.39 microM, respectively [20].

Associations of Quazepamum with other chemical compounds

• Itraconazole treatment did not change the plasma kinetics of quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoquazepam and N-desalkyl-2-oxoquazepam [21].
• The AUC ratio of OQ to quazepam was significantly lower in the fluvoxamine phase [22].
• The hypnotics, quazepam (a benzodiazepine), brotizolam (a thienotriazolodiazepine), zopiclone (a cyclopyrrolone) and zolpidem (an imidazopyridine) have a common ability to bind to the benzodiazepine recognition site (omega receptor) within the GABAA receptor [23].
• Neural-network pattern classifiers were used to study the effects of long half-life flurazepam (30 mg) and quazepam (15 mg), and short half-life triazolam (0.5 mg) on non-REM sleep [24].
• Indirect localization of the binding sites for quazepam and halazepam was accomplished by using the ability of these compounds to displace [3H]-flunitrazepam binding [25].

Gene context of Quazepamum

• CYP3A4 is the enzyme predominantly responsible for all the metabolic pathways of quazepam [20].
• In addition, CYP2C9 and CYP2C19 inhibitors failed to inhibit OQ formation from quazepam [20].
• The present study thus suggests that CYP 3A4 is partly involved in the metabolism of quazepam [21].
• Single oral dose pharmacokinetics of quazepam is influenced by CYP2C19 activity [26].
• Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after quazepam dosing [21].

Analytical, diagnostic and therapeutic context of Quazepamum

• In a randomized two-way crossover design, each subject received one 15-mg quazepam tablet either at night just before sleep or in the morning after a night's sleep [10].
• In the cerveau isolé, quazepam did not influence the typical synchronized EEG pattern [16].
• Sleep laboratory studies on human volunteers have shown quazepam 15 mg to be an effective hypnotic dose, with the 30-mg dose being optimal [27].
• In 18-day pregnant mice, concentrations of quazepam and its metabolites were measured either by gas-liquid chromatography or thin layer radiochromatography [28].
• Plasma concentrations of quazepam and its active metabolite 2-oxoquazepam (OQ) were measured by HPLC [26].

References