triazulenone and Sleep-Initiation-and-Maintenance-Disorders

Loprazolam is a 1,4-benzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia. As loprazolam has a half-life of 7 to 8 hours in healthy adults it may have advantages over longer-acting hypnotics, particularly when residual sedative effects on the day after ingestion are undesirable, although at doses greater than 1 mg residual sedation may occur. In addition, it may reduce daytime anxiety, following a hypnotic dose the night before, more effectively than the short-acting drug, triazolam. In short term comparative studies loprazolam was clearly superior to placebo, and was at least as effective as triazolam, flurazepam, nitrazepam, flunitrazepam or temazepam in hastening sleep onset, reducing nocturnal awakenings and increasing total sleep duration and quality. In the small number of patients with chronic insomnia who have received extended treatment with loprazolam, no evidence of tolerance has occurred, although rebound insomnia was evident 3 days after drug withdrawal in several studies. Thus, with its 'intermediate' elimination half-life, loprazolam would appear to have some potential advantages over both long- and short-acting hypnotics in selected patients, although further studies are needed to fully elucidate its place in therapy.

Topics: Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Humans; Kinetics; Nitrazepam; Sleep; Sleep Initiation and Maintenance Disorders; Triazolam

The aim of the study was to investigate the pharmacokinetic profile of acute and steady state doses of loprazolam (1 mg) following nighttime administration in 12 young (18-30 years) and 12 elderly (60-80 years) nonfasting subjects. Loprazolam blood plasma concentration was determined by high-performance liquid chromatography with ultraviolet absorption detection. The drug was isolated from the plasma using a solid phase extraction procedure. On day 1 subjects were breathalyzer and given a brief medical examination. Baseline blood samples (10 ml) were taken via a venous cannula at -1.5 to -0.25 h prior to drug administration. Loprazolam was administered at 21.00 and further blood samples were taken at 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 5, 6, 8, 10, 12, 18 and 23.5 h (baseline sample for day 2). On subsequent days (days 2, 3 and 4) blood samples were taken at -0.5 and 2 h. The schedule for day 1 was repeated for day 5 with the test period ending at 21.30 on day 6. Significant changes in the pharmacokinetics of the drug were evident in the elderly volunteers compared with the young volunteers following steady state, where tmax was significantly prolonged (CI 90% = 0.80 to 1.25; p < 0.00006) and a decline was observed in peak plasma concentration (CI 90% = 0.80 to 1.25; p < 0.00006). However, no statistically significant difference was found between the two groups in either the elimination half-life of the drug or the area under the curve. Loprazolam appears to be well tolerated by both the young and the elderly and only mild adverse effects were reported after nighttime administration. These results provide valuable data on the pharmacokinetics of the drug in normal clinical practice.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Anxiety Agents; Area Under Curve; Benzodiazepines; Biological Availability; Dizziness; Fatigue; Half-Life; Headache; Humans; Middle Aged; Sleep Initiation and Maintenance Disorders; Sleep Stages

1. This study compared two hypnotics administrated at comparable therapeutic dosages: triazolam (0.25 mg) and loprazolam (1 mg), were administered using an original scheme (cross-over on the first 2 nights, and continuation of the preferred treatment or new randomization). 2. Sixty-seven outpatients complaining of common insomnia participated in this study conducted by general practitioners. 3. Both drugs provided improvement in sleep quality (decreased sleep latency, increased total duration of sleep, decreased number of night awakenings), and are equally well tolerated. 4. For the first 2 nights, triazolam was evaluated to be more efficient than loprazolam (p < 0.001), and patients felt more rested the following day (p < 0.01) with the former drug. Moreover, triazolam is more frequently preferred than loprazolam by 47.7% and 29.2%, respectively, (p = 0.09). 5. No interaction was found between treatment and order of administration or specific effects and order of administration.

Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Female; Humans; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Triazolam

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Time Factors; Triazolam

One hundred and ninety-seven patients exhibiting a disturbed sleep pattern were recruited by thirty-five general practitioners into this single-blind randomized parallel group multicentre study. There were twelve patient withdrawals or drop-outs leaving sixty-one, sixty-three and sixty-one patients who, following 2 nights on placebo as baseline, completed 5 consecutive nights of treatment on loprazolam (1 mg), temazepam (20 mg) and placebo, respectively. Loprazolam and temazepam were found to have similar hypnotic activity with both treatments being superior to placebo. There was no statistical difference in the side-effect profile of the three treatment groups.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Headache; Humans; Male; Placebos; Random Allocation; Sleep Initiation and Maintenance Disorders; Sleep Stages; Temazepam

A multicentre, parallel group hospital study was carried out in 190 subjects with insomnia to compare the efficacy, incidence of hangover and the side-effects of loprazolam and nitrazepam. Following 2 nights single-blind phase on placebo, loprazolam (1.0 mg), nitrazepam (5.0 mg) or placebo was administered double-blind for 7 consecutive nights. Visual analogue scales and questions were used to rate efficacy. There was no statistically significant difference between loprazolam and nitrazepam for 'ease of getting to sleep', 'restfulness of sleep' and 'depth of sleep'. Like nitrazepam, loprazolam diminished the number of periods of wakefulness and made it 'easier to get to sleep again'. Subjective evaluation showed that hangover was not a feature of loprazolam. It did not affect morning alertness and patients thought they had improved balance and co-ordination while on this drug. These findings are in keeping with the evidence of other workers who have shown only minimal psychomotor impairment, if any, with loprazolam (1.0 mg). There was no statistically significant difference between treatments with respect to frequency or incidence of side-effects.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Nitrazepam; Sleep Initiation and Maintenance Disorders; Sleep Stages; Wakefulness

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Double-Blind Method; Drug Tolerance; Female; Humans; Longitudinal Studies; Male; Middle Aged; Sleep Initiation and Maintenance Disorders

Loprazolam is a benzodiazepine derivative which possesses, in animals, a potent hypnotic effect. In a double-blind single-dose study, three dose levels of loprazolam (0.5, 1.0, and 2.0 mg) were compared to each other as well as to 15 mg flurazepam and placebo in 60 insomniac outpatients. The 0.5- and 1.0-mg doses demonstrated hypnotic potency comparable to that of flurazepam, and all three treatments were superior to placebo. The hypnotic effect of the 2-mg dose of loprazolam was significantly greater than that of the other treatments, but at this dose, patients experienced significantly more side effects and morning hangover.

Topics: Adult; Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Double-Blind Method; Female; Flurazepam; Humans; Male; Middle Aged; Placebos; Sleep Initiation and Maintenance Disorders

Topics: Adult; Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Triazolam

A double-blind trial was carried out in 40 anxious in-patients with insomnia to compare the hypnotic effectiveness and tolerance of loprazolam, 1 mg and 2 mg, versus placebo. Groups of 10 patients received one or other dose of loprazolam or placebo for 7 nights and then placebo for the following 3 nights. Sleep quality and morning residual effects were assessed each morning during the 10-day trial period by means of a sleep questionnaire. The results showed that 1 mg loprazolam was superior to placebo but less effective than 2 mg loprazolam. No side-effects were reported at either dose level.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Random Allocation; Sleep Initiation and Maintenance Disorders

A double-blind, parallel group, randomized trial was carried out to compare the hypnotic efficacy of 1.0 mg loprazolam and 5.0 mg nitrazepam in 40 elderly patients. All had disturbed sleep patterns, which were not the result of physical illness, and had been shown to be placebo non-responders during a 3-day placebo screening period. Patients received active medication for 7 nights. Both loprazolam and nitrazepam significantly improved sleep patterns, as measured by patient self-rating scales and night nurses' global assessments, in comparison with the placebo baseline screen (p less than 0.001). No significant differences in efficacy were shown between drug treatments and no untoward effects were recorded which could be attributed to either drug. The results suggest that 1.0 mg loprazolam is an effective and well-tolerated hypnotic in elderly patients suffering from insomnia.

Topics: Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Nitrazepam; Random Allocation; Sleep Initiation and Maintenance Disorders; Time Factors

A double-blind crossover study was carried out in 16 patients with insomnia to assess the effectiveness and tolerance of a new hypnotic, loprazolam, with that of nitrazepam and placebo. Patients received 1 capsule each night for 7 days of either 1 mg loprazolam, 5 mg nitrazepam or placebo and then 7 days' treatment with each of the other medications in random order. The results of analogue rating scale assessment by the patients showed that 'ease of getting to sleep' and 'quality of sleep' were significantly better with loprazolam than with placebo. Loprazolam appeared to be at least as effective, if not more so, than nitrazepam. There were no significant differences between treatments on the morning muzziness assessment, which was low in each group, or in the psychometric tests carried out indicating that loprazolam is unlikely to produce hangover effects. There were no obvious differences between treatments in the incidence or frequency of side-effects spontaneously volunteered by the patients.

Topics: Adult; Aged; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Clinical Trials as Topic; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Nitrazepam; Psychomotor Performance; Sleep; Sleep Initiation and Maintenance Disorders

Topics: Adult; Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Humans; Sleep Initiation and Maintenance Disorders

Topics: Anti-Anxiety Agents; Benzodiazepines; Benzodiazepinones; Drug Tolerance; Female; Humans; Male; Sleep Initiation and Maintenance Disorders; Time Factors