Disease relevance of nitrazepam

• The mechanism of nitrazepam-induced drooling and aspiration [1].
• ygdP, a gene associated with the invasion of brain microvascular endothelial cells by Escherichia coli K1 (Badger, J. L., Wass, C. A., and Kim, K. S. (2000) Mol. Microbiol. 36, 174-182), the primary Gram-negative bacterium causing meningitis in newborns, has been cloned and expressed in E. coli [2].
• Clonazepam, a chlorinated derivative of nitrazepam, was administered to 10 children with absence seizures [3].
• Infantile spasms. Comparative trial of nitrazepam and corticotropin [4].
• Nitrazepam clearance unimpaired in patients with renal insufficiency [5].

Psychiatry related information on nitrazepam

• Rebound insomnia, a worsening of sleep compared with baseline, occurred following withdrawal of triazolam, nitrazepam, and flunitrazepam after they had been given in only single, nightly doses for short periods [6].
• Depersonalization following nitrazepam withdrawal [7].
• Paradoxical response to nitrazepam in a patient with hypersomnia secondary to nocturnal myoclonus [8].
• In contrast, nitrazepam impaired psychomotor performance and standing steadiness as the serum drug levels increased [9].
• Changes in reaction time and drug plasma concentrations after nitrazepam and glutethimide [10].

High impact information on nitrazepam

• Gene ablation studies have revealed a requirement for Stat3 in diverse biological processes (Akira, S. 2000. Oncogene. 19: 2607-2611; Levy, D.E., and C.K. Lee. 2002. J. Clin. Invest. 109:1143-1148) [11].
• We have cloned the ACD2 gene; its predicted product shows significant and extensive similarity to red chlorophyll catabolite reductase, which catalyzes one step in the breakdown of the porphyrin component of chlorophyll [Wüthrich, K. L., Bovet, L., Hunziger, P. E., Donnison, I. S. & Hörtensteiner, S. (2000) Plant J. 21, 189-198] [12].
• Superoxide and lipid free-radical generation in cultured endothelial cells treated with menadione or nitrazepam were measured using electron paramagnetic resonance spectroscopy [13].
• The nitro anion free radical of reduced nitrazepam, which cannot cross the plasma membrane, did not generate detectable extracellular superoxide [13].
• Although the role of the C-terminal Cav1 binding domain is not known, its deletion did not affect localization of TRPC1 (Singh, B. B., Liu, X., and Ambudkar, I. S. (2000) J. Biol. Chem. 275, 36483-36486) [14].

Chemical compound and disease context of nitrazepam

• No rebound insomnia was evident during a 7 day post-treatment withdrawal period for either zopiclone or nitrazepam [15].
• Eight patients with mild to moderate renal insufficiency (mean serum creatinine: 2.4 mg/100 ml) and 9 matched control subjects with normal renal function received a single 5-mg oral dose of nitrazepam, cleared mainly by hepatic nitroreduction [5].
• Escherichia coli GDP-mannose mannosyl hydrolase (GDPMH), a homodimer, catalyzes the hydrolysis of GDP-alpha-D-sugars to yield the beta-D-sugar and GDP by nucleophilic substitution with inversion at the C1' carbon of the sugar [Legler, P. M., Massiah, M. A., Bessman, M. J., and Mildvan, A. S. (2000) Biochemistry 39, 8603-8608] [16].
• Three benzodiazepines, nitrazepam, diazepam and chlordiazepoxide administered orally, potentiated the effect of muscimol (30 ng) injected into the globus pallidus and induced catalepsy [17].
• 3 Both chlormezanone and nitrazepam initially caused increase of sleep duration and less interruption of sleep by wakefulness [18].

Biological context of nitrazepam

• Previously, we reported that double-strand DNA breaks can be enzymatically produced from two DNA damages located on opposite DNA strands 18 or 30 base pairs apart in a cell-free double-strand DNA break formation assay (Vispé, S., and Satoh, M. S. (2000) J. Biol. Chem. 275, 27386-27392) [19].
• Recently it was shown that the NH(2)-terminal domain of the Dfp protein from bacteria catalyzes the next step in CoA biosynthesis, the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to form 4'-phosphopantetheine (Kupke, T., Uebele, M., Schmid, D., Jung, G., Blaesse, M., and Steinbacher, S. (2000) J. Biol. Chem. 275, 31838-31846) [20].
• Previously, we noted that inorganic phosphate (P(i)), a major component of bone extracellular matrix, induced osteoblast apoptosis (Meleti, Z., Shapiro, I. M., and Adams, C. S. (2000) Bone (NY) 27, 359-366) [21].
• Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose [22].
• Polymorphic acetylation of nitrazepam [23].

Anatomical context of nitrazepam

• In contrast, growth inhibition was observed when high concentrations of gangliosides were continuously present in the culture medium during incubation of fibroblasts with growth factors (Li, R., Manela, J., Kong, Y., and Ladisch, S. (2000) J. Biol. Chem. 275, 34213-34223) [24].
• DEDMPO was used to determine if hydroxyl radical was produced during the metabolism of menadione or nitrazepam by porcine thoracic aorta endothelial cells [25].
• 2 Manifestations of unwanted central nervous system (CNS) depression (such as drowsiness or 'hangover') were reported in 49 nitrazepam recipients (2.3%), and signs of unwanted CNS stimulation (such as nightmares, insomnia, agitation, etc.) in 15 (0.7%) [26].
• The average amount of nitrazepam received by the breast-fed baby in the morning was calculated to increase from 1 to 1.5 micrograms 100 ml-1 breast milk, from days 1 to 5 [27].
• The efficacy of zaleplon for the competitive inhibition of [(3)H]flunitrazepam binding to the membrane preparation from hippocampus was thus less than that of triazolam and nitrazepam [28].

Associations of nitrazepam with other chemical compounds

• Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered [22].
• A new pathway for triacylglycerol biosynthesis involving a phospholipid:diacylglycerol acyltransferase (PDAT) was recently described (Dahlqvist A, Stahl U, Lenman M, Banas A, Lee M, Sandager L, Ronne H, Stymne S, [2000] Proc Natl Acad Sci USA 97: 6487-6492) [29].
• Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice [15].
• Studies were then undertaken to exploit the hydroxylamine/nitroso redox couple using LC-DED detection for the measurement of nitrazepam in serum [30].
• GDP-mannose mannosyl hydrolase (GDPMH) is an unusual Nudix family member, which catalyzes the hydrolysis of GDP-alpha-D-mannose to GDP and the beta-sugar by nucleophilic substitution at carbon rather than at phosphorus (Legler, P. M., Massiah, M. A., Bessman, M. J., and Mildvan, A. S. (2000) Biochemistry 39, 8603-8608) [31].

Gene context of nitrazepam

• Although cloxazolam was a potent and specific inhibitor of AKR1C3, diazepam, estazolam, flunitrazepam, medazepam and nitrazepam, that inhibited AKR1C1 and AKR1C2, may influence the neurosteroid metabolism [32].
• Among the 5 non-conserved residues within this segment, Arg-142 in human and Gln-142 in mouse ADA largely determined the capacity for stable binding to CD26 (Richard, E., Arredondo-Vega, F. X., Santisteban, I., Kelly, S. J., Patel, D. D., and Hershfield, M. S. (2000) J. Exp. Med. 192, 1223-1235) [33].
• In addition to PAPS, phenol sulfotransferase (PST), a member of the ST family, utilizes other nucleotides as substrates with much less catalytic efficiency [Lin, E. S., and Yang, Y. S. (2000) Biochem. Biophys. Res. Commun. 271, 818-822] [34].
• We have previously shown (Nuti, S. L., Mehdi, A., and Rao, U. S. (2000) Biochemistry 39, 3424-3432) that tryptic cleavage of Pgp results in the activation of basal and drug-stimulated ATPase functions of Pgp [35].
• Recently, the propeptide domain of the prototype membrane type matrix metalloproteinase (MT1-MMP) was demonstrated to act as an intramolecular chaperone (Cao, J., Hymowitz, M., Conner, C., Bahou, W. F., and Zucker, S. (2000) J. Biol. Chem. 275, 29648-29653) [36].

Analytical, diagnostic and therapeutic context of nitrazepam

• Serum nitrazepam levels were determined by gas chromatography during the 72 hours after dosage [5].
• Voltammetric behavior of nitrazepam and its determination in serum using liquid chromatography with redox mode dual-electrode detection [30].
• Fifty-two patients were enrolled in a four-week randomized multicenter study comparing nitrazepam and corticotropin in the treatment of infantile spasms [4].
• The hypnotic effects, effects on psychomotor performance, EEG activity and standing steadiness between BAHS 1000 mg and nitrazepam 5 mg were compared at regular intervals for 10 h [9].
• The neutral to base transition in human serum albumin has been studied by means of circular dichroism and equilibrium dialysis using nitrazepam as the non-covalently bound circular dichroic probe [37].

References