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PubMed1977

[Effects of 5-(o-chlorophenyl)-1-methyl-7-nitro-1, 3-dihydro-2HO1, 4-benzodiazepin-2-one (ID-390) as compared to nitrazepam on the sleep-wakefulness cycle in cats (author's transl)].

ID-690 was given at doses over 0.3 mg/kg, and increase in state of arousal and decrease in state of slow wave sleep were observed. Nitrazepam at doses over 1.0 mg/kg revealed similar effects. These agents increased incidences of paradoxical sleep at a low dose of 0.03 mg/kg. When ID-690 was given at doses over 0.3 mg/kg, the number and duration of incidences of paradoxical sleep decreased. Nitrazepam at doses over 0.1 mg/kg had a similar depressive effect on paradoxical sleep. These results suggest that these benzodiazepines have, dose-dependently, both facilitative and depressive actions on paradoxical sleep, and that the dose of these agents which affects arousal is not always the same as that which affects paradoxical sleep.

Animals↗
PubMedDate not supplied

1H-NMR investigations on the hydrogen bond formation between the tranquilizers diazepam and nitrazepam and some nucleobases.

The formation of hydrogen bonds between the minor tranquilizers diazepam and nitrazepam and a few nucleobases was studied in deuterochloroform solution by means of proton magnetic resonance spectroscopy. The thermodynamic and spectroscopic data of the associations were evaluated on the basis of a dimer model, using the concentration dependent shifts of the protons involved in hydrogen bonds. The interactions of nitrazepam (deltaH0=-10 to -21 kJ/mol; deltaG025 -0.2 to -7.4 kJ/mol) were found to be stronger than those of diazepam (deltaH0=-10 to -13 kJ/mol; deltaG025=6.0 to 6.4 kJ/mol). The various binding sites of the benzodiazepines for hydrogen bonds are discussed.

Adenine↗
PubMed1989

Double-blind study on the hypnotic and antianxiety effects of zopiclone compared with nitrazepam in the treatment of insomnia.

The effects of zopiclone (7.5 mg/per os/day), a new non-benzodiazepine drug, on anxiety levels, time of sleep induction, hours of sleep, number of nocturnal arousals, quality of sleep and of daytime arousal were evaluated by using psychometric ratings. A random double-blind cross-over study versus nitrazepam (5.0 mg/per os/day) was performed on 20 patients affected by insomnia and generalized anxiety disorder (DSM III-R). The effects were evaluated by using the Hamilton Rating Scale for Anxiety, the Toulouse-Pieron Attention Test and a time-signed quantitative scale for anxiety. The results of the trial confirmed the effectiveness of zopiclone in the treatment of insomnia with effects similar to nitrazepam on the quality and duration of sleep and number of nocturnal arousals, but with an improvement in all the other parameters.

Adult↗
PubMed1989

[Daytime sedation measured after intake of nitrazepam and lorazepam, respectively, as hypnotics for 10 days].

A prospective double-blind cross-over investigation was undertaken among 46 geriatric patients (62-92 years) in which either 5 mg nitrazepam or 1 mg lorazepam were administered as hypnotics for two periods of ten days. No significant differences were observed in the quality of sleep but the objective psychomotor tests and the patients' subjective experience of hang-overs showed that there were significant differences in the frequencies of side effects in favour of lorazepam. It is concluded that daytime sedation after repetitive administration of a benzodiazepine preparation depends upon the half-life and that side effects are revealed better by psychomotor tests than by intellectual, cognitive tests and that lorazepam should be given preference to nitrazepam as a hypnotic for elderly patients.

Aged↗
PubMedDate not supplied

[Influence of antidepressants on benzodiazepine (diazepam and nitrazepam) effects].

Inkazan and pyrazidol given to mice in certain doses were found to reduce the sedative action of diazepam without decreasing its anxiolytic effect but at the same time enhancing the anticonvulsive one. Imipramine diminishes the hypolocomotor action of diazepam and also its anxiolytic effect and exerts no influence on the anticonvulsive effect. All studied antidepressants diminish the hypnotic action on nitrazepam in mice but only inkazan and pyrazidol decrease the sedative-hypnotic effect of nitrazepam in rats. In connection with the lack of the influence on the anxiolytic effect, inkazan and pyrazidol may be used to decrease the sedative side effects of benzodiazepines.

Animals↗
PubMed1977

Long term study of hypnotic medication in geriatric patients. A study of dixyrazine, nitrazepam and amylobarbitone.

The hypnotic effect of dixyrazine (a phenothiazine derivate), nitrazepam and amylobarbitone was studied during six months in 52 geriatric inpatients (17, 16 and 19 in each group, respectively) with a mean age of 78 years. The variables registered were the percentage of patients asleep at 10 pm and 6 am and the observed number of awakenings. Certain mental and somatic variables were rated according to a schedule for geriatric behaviour. The observations were made every two to three weeks. No systematic significant change with time was observed for any of the three drugs for the percentage of patients asleep at 10 pm or 6 am or for the number of awakenings. Nor was any difference found between the three drugs in respect of these variables. There was no significant change in somatic or mental variables according to the geriatric rating schedule. The results indicate that dixyrazine, nitrazepam and amylobarbitone retain their hypnotic effect in geriatric patients during continuous use for a six-month period. No side effects were observed that influenced the patient' behaviour. The results do not support the view that barbiturates, i.e. amylobarbitone are inappropriate as hypnotics in the elderly patient.

Aged↗
PubMed1987

Chronic administration of zopiclone and nitrazepam in the treatment of insomnia.

The hypnotic effects of 7.5 mg zopiclone, as well as its unwanted and residual effects, were compared with those of 5 mg nitrazepam in a double-blind, randomized, multicenter, parallel group study. After an initial, 7-day, placebo wash-out period, insomniac out-patients under the care of general practitioners received either 7.5 mg zopiclone or 5 mg nitrazepam for 6 weeks. Everyday, the patients filled in a diary (analogue scales for sleep parameters and condition during daytime); a sleep questionnaire was filled in at baseline and at the end of active treatment period; every 2 weeks, a somatic complaint check-list inventory and a mood rating scale were filled in and psychomotor tests performed; and at the end of the study, a global evaluation of efficacy and acceptability was given by the investigator. Clinical laboratory tests were performed before and after the active treatment period. From the diary, sleep onset latency, as well as sleep quality, were similarly improved by both drugs throughout the whole study. From the sleep questionnaire, all sleep parameters measured were improved at the end of the 6-week treatment period in both groups. No statistical differences in the various psychomotor tests were observed between the two treatment groups, and a significant improvement in the working ability of patients was noted with both drugs. Some significant differences were observed in the mood rating scale and the somatic complaint check list, probably related to differences in pharmacokinetics of the two drugs.

Adolescent↗
PubMed1987

Complications in correlation studies between serum, free serum and saliva concentrations of nitrazepam.

The relation between free serum and saliva concentrations of nitrazepam in healthy male volunteers has been studied. It was found that the average value of free serum concentrations from all volunteers was twice the average value of corresponding saliva concentrations. Sometimes mean values of serum, free serum and saliva concentrations are used in correlation studies. However, the data from individual volunteers showed that there was no correlation between them. Statistics can easily introduce false pictures for correlations between free serum and saliva concentrations of nitrazepam, whereas no correlation could be found on the basis of results from individuals. In response studies such as the effects of drugs on driving performance, the free serum and saliva concentrations of a drug from individual volunteers should therefore be considered. This will complicate the use of saliva in epidemiological studies on drugs and driving.

Adult↗
PubMedDate not supplied

Enhancement of reductive metabolism of p-nitrobenzoate and nitrazepam in isolated perfused rat liver by ethanol.

Reductive metabolism of p-nitrobenzoate (2 mM) was studied in the isolated perfused rat liver, after acute ethanol dosing, with use of a hemoglobin-free perfusion medium. Formation of reduced metabolites under control conditions (0.3 mumol per g of liver per hr) was enhanced fivefold (1.4 mumol/g/hr) in the presence of ethanol (38 mM), thus reaching hepatic reductase activities occurring under anaerobic conditions (1.4 mumol/g/hr). Ethanol failed to increase hepatic nitro reduction when alcohol dehydrogenase was inhibited by pyrazole. Addition of acetaldehyde led to a marked stimulation of nitroreductase activity. Carbon monoxide did not influence the ethanol-mediated enhancement of nitroreductase activity but almost abolished the enhancement caused by anoxia. Reductive azo cleavage of salazosulfamide was not enhanced by ethanol. When nitrazepam was used as the substrate (1 mM) for the isolated perfused rat liver, addition of ethanol (38 mM) led to an enhanced content of 7-amino derivative in the liver and in the perfusate, whereas the formation of 7-acetylamino derivative remained unchanged. The distribution of nitrazepam in liver and perfusate was not altered by ethanol.

Animals↗
PubMed1980

The effects of triazolam and nitrazepam on sleep quality, morning vigilance and psychomotor performance.

1. Repeated doses of triazolam 0.5 mg and mitrazepam 10 mg were given to two groups of consenting volunteers. 2. Measures of choice reaction time, critical flicker fusion threshold, and mental arithmetic ability were made the morning following nocturnal medication with either the active drug or placebo. 3. The subjects' assessment of sleep and early morning behaviour were obtained on 10 cm-line visual analogue scales. 4. Both drugs were rated as effective hypnotics while, at the same time, ratings of the ease of awakening from sleep and the errors produced in a mental arithmetic task were impaired. 5. Objective measures of performance and subjective reports of "hangover" differentiated nitrazepam from triazolam. A significant impairment of early morning performance found with nitrazepam was not found following treatment with triazolam.

Adult↗
PubMed1983

An evaluation of the short-term hypnotic efficacy of loprazolam in comparison with nitrazepam in elderly patients.

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.

Aged↗
PubMed1982

Comparison of nitrazepam and zopiclone in psychiatric patients.

This investigation compares the effects of single and double doses of nitrazepam (5 and 10 mg) and zopiclone (7.5 and 15 mg) and placebo for 1 night in 40 psychiatric patients. The results indicate that zopiclone is an active hypnotic compound, comparable in its effects to those of nitrazepam, the higher dosage being best adapted to the type of patients included in the study.

Adolescent↗
PubMed1980

[Reduction of nitrazepam by rat liver mitochondria (author's transl)].

Highly purified rat liver mitochondria are able to reduce nitro groups of organic compounds to primary amines. This reductase-activity is bound to mitochondrial inner membrane or its matrix. It has no plain substrate specificity whereas it will attack the various substrates at widely different rates [nitrazepam (Mogadan) 1.7 times faster than 4-nitrobenzoic acid]. The activity was markedly inhibited under aerobic conditions. The rate of nitrazepam reduction by rat liver mitochondria was about 1/3--1/4 the rate by microsomal fraction, provided that both preparations contained the same protein amounts. NADH was required as a cofactor, but the nitroreduction was also stimulated by some Krebs cycle intermediates, especially by alpha-ketoglutarate. The reaction was markedly inhibited by organic solvents, even by little volumes. DMSO and DMF are cancelling every activity.

Animals↗
PubMed1993

[Determination of benzodiazepines by thermospray liquid chromatograph-mass spectrometer. Part 1. Nitrazepam, estazolam, bromazepam, flunitrazepam].

Thermospray liquid chromatography mass spectrometric method is described for the determination of the benzodiazepines (Nitrazepam, Estazolam, Bromazepam, Flunitrazepam). Reversed-phase liquid chromatography was performed using a 15 cm Shim-pack CLC-ODS (Shimadzu) column, with acetonitrile-water (40:60) + 0.1 M ammonium acetate as mobile phase, at a flow rate of 1.0 ml/min. The temperature of the vaporizer, block and TH of the source block were 166, 270 and 275 degrees C, respectively. Positive ion thermospray mass spectra by thermospray ionization (TSP ionization) mode or thermospray on filament ionization (filament-on ionization) mode were obtained. Formation of the MH+ ion was observed as a base peak under TSP ionization and filament-on ionization conditions and fragment ions were very few. On both ionization mode, peaks representing nitrazepam as MH+ at m/z 282 at a retention time (R.T.) of 6.4 min, from estazolam as MH+ at m/z 295 at an R.T. of 6.4 min, from bromazepam as MH+ at m/z 316 at an R.T. of 4.5 min and from flunitrazepam as MH+ at m/z 314 at an R.T. of 8.8 min. The detection limit for all the benzodiazepines under investigation was less than 0.5 ng (S/N = 9.4 +/- 4.6) using selected ion monitoring.

Benzodiazepines↗
PubMedDate not supplied

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease. The effect of premedication with cystamine on pharmacodynamics and Pharmacokinetics of nitrazepam.

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease (I). Effect of premedication with cystamine on pharmacodynamics and pharmacokinetics of nitrazepam. Acta Physiol. Pol. 1977, 28 (2): 161--168. In the experiments carried out on rats the radiation disease was evoked by exposure to 600 R. The strongest radioprotective action of cystamine was found on the 3-rd day of radiation disease. The tendency to normalization of both the pharmacodynamics (exploring mobility and anticonvulsant action) and pharmacokinetics of nitrazepam in the animals premedicated with cystamine was described.

Animals↗
PubMed1977

Influence of cystamine on pharmacokinetics and pharmacodynamics of nitrazepam.

The influence of cystamine on pharmacokinetics of nitrazepam was studied. Experiments were performed on the third day after the administration of cystamine, since the author's previous investigations showed that the protective action of cystamine in radiation sickness was strongest at this time. CA premedication resulted in more rapid resorption, lower level of nitrazepam in blood, and more rapid elimination of the drug.

Animals↗
PubMed1977

The influence of alcohol on the persistent effects on human performance of the hypnotics Mandrax and Nitrazepam.

Psychotropic drugs are prescribed to modify human behavior but they have persistent central sedative activity which may become a troublesome side-effect. Alcohol is known to interact with psychotropes, often to potentiate their central effects. We have previously shown that residues of some hypnotic drugs persist in the body for up to a week after a single therapeutic dose and have demonstrated that alcohol decreases the elimination rate of methaqualone even when taken 2 or 3 days after the drug. We have therefore looked at the influence of alcohol on the residual effects of Mandrax and nitrazepam on three measurements of human performance. The study was a double-blind, 3-way, cross-over study in which the following treatments were used: drug + alcohol, drug + alcohol placebo, and drug placebo + alcohol. In each case the alcohol or alcohol placebo was given 1, 2, and 3 days after the drug or placebo. The subject's kinetic visual acuity was measured 40 minutes after the alcohol had been taken. This was followed by a Stroop test. Changes in mental state and arousal were measured by an 18-item visual analogue scale. An interaction between alcohol and Mandrax was apparent in the results obtained from the Stroop and visual analogue scale on the third day. However, no interaction with nitrazepam could be clearly demonstrated by any of the tests on any occasion. The application of these results to the "real life" situation is discussed.

Adult↗
PubMed1971

Nitrazepam in the treatmet of epilepsy in childhood.

The anticonvulsant activity of nitrazepam (Mogadon) was studied in 31 children with various seizure patterns. Dosage ranged from 0.3 to 2.2 mg. per kg. body weight daily.Eleven of 15 children with minor motor seizures showed improvement and six obtained complete relief. Nine of 16 with miscellaneous seizures were improved, but only one was completely relieved and the other eight responded to a variable extent. In cases with more than one type of seizure, the myoclonic elements were those most often diminished, but sometimes this effect was only temporary. Side effects were transient and usually mild, consisting of drowsiness, ataxia, slurred speech and excessive secretion of mucus and saliva. However, three cases of aspiration pneumonia were encountered and may have been at least partly due to the side effects. No hematological or biochemical abnormalities were observed.The results indicate that nitrazepam is a relatively safe and effective drug in the treatment of minor motor seizures, particularly infantile spasms, and is even more useful than ACTH in this serious form of epilepsy. In older children its value is chiefly for myoclonic seizures, but the degree and duration of its effectiveness appear to be more limited.

Adolescent↗