Disease relevance of Seduxen

• Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001) [1].
• Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesses [2].
• Diazepam to prevent febrile seizures [3].
• Propylene glycol toxicity in a patient receiving intravenous diazepam [4].
• Of the 153 children who took at least one dose of diazepam, 39 percent had ataxia, lethargy, or irritability or at least one other moderate side effect that was reversed after a reduction in the dose [2].

Psychiatry related information on Seduxen

• Interaction between purine and benzodiazepine: Inosine reverses diazepam-induced stimulation of mouse exploratory behavior [5].
• Withdrawal symptoms after six weeks' treatment with diazepam [6].
• Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam [7].
• Patients with panic disorder were less sensitive than controls to diazepam using eye velocity as the dependent measure [8].
• Diazepam given under this regimen is a safe and effective sedative for management of combative patients with severe delirium tremens [9].

High impact information on Seduxen

• We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures [10].
• The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08) [1].
• Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo [11].
• An analysis restricted to children who had seizures while actually receiving the study medication (7 in the diazepam group and 29 in the placebo group) showed an 82 percent reduction in the risk of febrile seizures with diazepam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.37; P < 0.001) [2].
• Cimetidine is known to impair the hepatic microsomal oxidation of diazepam, reducing its clearance and prolonging its half-life [12].

Chemical compound and disease context of Seduxen

• Potentiation of lonidamine and diazepam, two agents acting on mitochondria, in human glioblastoma treatment [13].
• Letter: Diazepam, phenytoin, and aetiology of cleft lip and/or cleft palate [14].
• The pattern of the visual evoked potential in hepatic coma (due to galactosamine-induced fulminant hepatic failure) differed fundamentally from that in ether-induced coma, but was identical to that in comas induced by three drugs which activate gamma-aminobutyric acid-ergic neural mechanisms: pentobarbital, diazepam, and muscimol [15].
• Fatal bradycardia after intentional overdose of cimetidine and diazepam [16].
• Panic attacks and phobic symptoms responded to diazepam, but not to propranolol [17].

Biological context of Seduxen

• The data suggest that first-trimester exposure to diazepam does not materially affect the risk of cleft lip with or without cleft palate or of cleft palate alone [18].
• Diazepam induces mitotic arrest at prometaphase by inhibiting centriolar separation [19].
• The enhancement of diazepam binding results from a rapid increase in the number of available binding sites rather than a change in receptor affinity [20].
• Characteristic potentiation of rat locomotion responses and acoustic startle reflexes that normally appear in the third postnatal week was absent in rats exposed to diazepam during the third week of gestation [21].
• The anxiolytic action of diazepam was absent in mice with the alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation [22].

Anatomical context of Seduxen

• Diphenylhydantoin: pre- and postnatal administration alters diazepam binding in developing rat cerebral cortex [23].
• The effect of diazepam on muscle cells in culture is direct and specific [24].
• Diazepam inhibits myoblast fusion and expression of muscle specific protein synthesis [24].
• Peripheral benzodiazepine receptors are localized to mitochondria and enriched in several endocrine glands where they are influenced by therapeutic blood levels of benzodiazepines such as diazepam [25].
• Quantitative analysis of CD4+ T cell function in the course of human immunodeficiency virus infection. Gradual decline of both naive and memory alloreactive T cells [26].

Associations of Seduxen with other chemical compounds

• In consequence, alpha 6(Q100)beta 2 gamma 2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Ro15-4513 [27].
• The voltage-clamp technique was then used to measure properties of the GABA-induced membrane currents and to study the effects of various modulators of the GABAA receptor channel (diazepam, DMCM, pentobarbital, and picrotoxin) [28].
• Omeprazole given orally in a daily dose of 40 mg over 7 days decreased diazepam plasma clearance from 22.4 +/- 2.8 to 10.1 +/- 1.5 ml/kg X h and prolonged the half-life of diazepam from 36.9 +/- 4.1 to 85.0 +/- 14.7 h [29].
• ES cell-derived hepatocytes expressed liver-specific genes, secreted albumin and metabolized ammonia, lidocaine and diazepam [30].
• Two hundred forty-one outpatients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam, diazepam, imipramine hydrochloride, and placebo [31].

Gene context of Seduxen

• CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia [32].
• Diclofenac (CYP2C9), diazepam (CYP2C19) and nifedipine (CYP3A4) were chosen for coadministration with ximelagatran in healthy volunteers [33].
• Fluoxetine increases the plasma concentrations of alprazolam and diazepam by inhibiting CYP3A and CYP2C19, respectively [34].
• In adult liver preparations, the hydroxylation of diazepam correlated well with the CYP3 A content of microsomes (r = 0.858, p < 0.01) and with the 6 beta hydroxylation of testosterone (r = 0.830, p < 0.005), whereas demethylation was related to the bulk of CYP2C proteins (r = 0.865, p < 0.005) [35].
• CYP2C19 and CYP1A2, the metabolism of several benzodiazepines, including alprazolam, bromazepam and diazepam [34].

Analytical, diagnostic and therapeutic context of Seduxen

• The hypothesis that in utero exposure to diazepam increases the risk of oral-cleft anomalies was evaluated in a case-control study, in which 445 infants with cleft lip with or without cleft palate and 166 with cleft palate without cleft lip (cleft palate alone) were compared with 2498 control infants having other birth defects [18].
• Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001) [11].
• Diazepam (Valium) dosage (5 milligrams per kilogram of body weight) during the period ow withdrawal serves to maintain undiminished such alcohol self-administration [36].
• The entire group of 43 visited doctors reduced the rate of long-term diazepam users in their practice by 18% relative to the control group; the subgroup of doctors who utilized the withdrawal schedule had and even greater reduction of 33% [37].
• This double-blind study involved the continuous (six to 22 weeks) treatment of 180 chronically anxious outpatients with diazepam, 15 to 40 mg/day [38].

References