Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical safety evaluation of the benzodiazepine quazepam. 289 Mar 57

The efficacy and safety of 15 mg quazepam was compared with placebo in 57 geriatric outpatients with insomnia. The study was double-blind, with treatments randomly assigned to patients. Placebo was taken by all patients for the first 3 nights followed by either placebo or quazepam for 5 nights. Post-sleep questionnaires were completed each day and the physician and patients rated the treatment at the end of the study. Quazepam was significantly better than placebo on all measures of efficacy. Indices of sleep quantity and quality showed that 15 mg quazepam produced significantly greater improvement in sleep than placebo on the first night of treatment and for the treatment period as a whole. There were no reports of unexpected or serious adverse experiences, and quazepam did not cause ataxia or impairment of motor co-ordination in any patient.
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PMID:Short-term quazepam treatment of insomnia in geriatric patients. 612 41

7-Chloro-1-(2,2,2-trifluoroethyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1, 4-benzodiazepine-2-thione (Sch 16134, quazepam) is a new hypnotic drug with demonstrated clinical efficacy. Quazepam has been shown in our laboratories to have potent hypnotic activity and fewer side effects at effective doses than flurazepam, which was studied concurrently. Hypnotic potency was estimated in mice via antagonism of electroshock-induced convulsions (ECS), potentiation of hexobarbital-induced sleeping time, and chlorprothixene potentiation. The respective oral ED50's (95% fiducial limits) in the 3 tests were 0.9 (0.4-2.0), 0.5 (0.3-0.8) and 0.05 (0.02-0.08) mg/kg for quazepam and 1.6 (1.1-2.3), 0.6 (0.4-1.0) and 0.11 (0.07-0.42) mg/kg for flurazepam. The duration of action of quazepam as measured by antagonism of ECS in mice was similar to that of flurazepam at equi-effective doses but quazepam had a faster onset. When potential tolerance to hypnotic efficacy was studied, quazepam did not show tolerance after dosing 20 mg/kg p.o. twice daily (b.i.d.) for 5 days, whereas tolerance was seen with flurazepam at equi-effective doses b.i.d. for 5 days. In conscious, unrestrained squirrel monkeys and cats, quazepam produced sedation with less ataxia and less evidence of CNS stimulant action than flurazepam. On the basis of the aforementioned studies, quazepam should be an effective hypnotic with less potential for ataxia, paradoxical excitation, and tolerance than flurazepam.
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PMID:The sedative-hypnotic properties of quazepam, a new hypnotic agent. 612 56

The hypnotic effect and tolerance of quazepam (Sch 16134) 15 and 30 mg, flunitrazepam 1 and 2 mg and placebo were evaluated in a one-night, randomized, double-blind, parallel group study of 100 hospitalized patients, who were to undergo a planned operation on the following day. All active drugs were rated as superior to placebo by the physician. Subjectively, quazepam 30 mg and flunitrazepam 1 and 2 mg were superior to placebo. Hangover effects were not distinguishable from placebo. Vigilance and ataxia tests were not altered by any of the drugs.
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PMID:Comparison of quazepam, flunitrazepam and placebo as single-dose hypnotics before surgery. 613 25