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At least 19 recordsLinked to original sources
PubMed1977

Serum medazepam, diazepam, and N-desmethyldiazepam levels after single and multiple oral doses of medazepam.

20 mg of medazepam were taken by mouth by 9 healthy volunteers in an acute absorption study. About a 10-fold variation was found during the first 6 hours after the drug in individual serum medazepam, diazepam, and N-desmethyldiazepam levels. In a subacute study 10 mg of medazepam t.i.d. was given to 10 institutionalized mentally subnormal adults with emotional disorders. After 14 days' treatment serum N-desmethyldiazepam levels were generally above 800 ng/ml, 7 to 8 times higher than the serum medazepam or diazepam levels measured 12 hours after the last dose. No correlation was observed between the serum concentration and efficacy of medazepam.

Administration, Oral↗
PubMedDate not supplied

Further studies on medazepam metabolism in the rat.

Previous studies with 9000g supernatant fractions of rat liver revealed that the 1,4-benzodiazepine, medazepam, was converted to N-desmethyldiazepam by a series of reactions including hydroxylation, N-demethylation, and dehydrogenation. The present study was designed to determine if the pathway via diazepam as intermediate, which is one of three possible pathways, is the major route in vivo in the rat for N-desmethyldiazepam formation from medazepam. Measurement of the levels of labeled drug and metabolites in blood, brain, lung, heart, and muscle 5 min after the oral administration of approximately equivalent doses of [14C]medazepam hydrochloride, [14C]diazepam, or N-desmethyl[14C]medazepam revealed that each drug was both rapidly absorbed and oxidatively metabolized in the rat. At 1 hr. the tissue levels of labeled N-desmethyldiazepam were highest after N-desmethyl-[14C]medazepam, intermediate after [14C]medazepam hydrochloride and lowest after [14C]diazepam. These results indicated that in the formation of N-desmethyldiazepam from medazepam in the rat there is a substantial preference for the pathway via N-desmethylmedazepam over that in which diazepam is an intermediate. From consideration of the limited data available, it is suggested that this same preference in pathways may also hold true in humans.

Animals↗
PubMed1990

Effect of the combination of the benzodiazepine tranquilizer medazepam and the nootropic agent meclofenoxate on the activity of rat brain muscarinic receptors.

1. The effect of 7-day treatment with the benzodiazepine tranquilizer medazepam (5 mg/kg), the nootropic agent meclofenoxate (100 mg/kg) and their combination in the same doses on the binding activity of muscarinic receptors in four rat brain structures (cerebral cortex, striatum, hippocampus and hypothalamus) were studied using the antagonist [3H]-1-quinuclidinyl benzylate [( 3H]-QNB) as radio-ligand. 2. Medazepam treatment caused significant decrease of muscarinic receptor binding affinity (Kd) and of the receptor binding capacity (Bmax) in the brain structures studied. The number of muscarinic binding sites was unsignificantly decreased only in the hippocampus. 3. Meclofenoxate treatment caused an increase of muscarinic receptor affinity and a decrease of the binding capacity in the cerebral cortex and hypothalamus and an increase of the binding affinity in the striatum and hippocampus. 4. The combination of medazepam and meclofenoxate caused no significant changes of both muscarinic receptor characteristics in the hippocampus and of the receptor affinity in the striatum and hypothalamus in comparison with control rats. The Bmax values were decreased in the cerebral cortex, striatum and hypothalamus when compared with control animals. The differences observed were slighter than those determined after the comparison of medazepam treated rats with control rats. 5. The results obtained afford an opportunity to suggest that the nootropic agent meclofenoxate acts to moderate the effect of the benzodiazepine tranquilizer medazepam on the activity of rat brain muscarinic receptors.

Animals↗
PubMed1979

Plasma concentrations of medazepam and its metabolites after oral administration.

The plasma concentrations of medazepam and its metabolites, diazepam and desmethyldiazepam, were determined in volunteer subjects following the oral administration of medazepam 10 mg. The results indicated that medazepam was absorbed rapidly, that low concentrations of metabolites were present during the 1st h, and that the build-up in the circulation of the major metabolite, desmethyldiazepam, was prolonged and variable. As many of the clinical effects and possible adverse reactions of medazepam appear to be associated with the presence of this major metabolite, the metabolic and pharmacokinetic characteristics of the drug should be considered when using medazepam as an anxiolytic before dentistry or surgery.

Administration, Oral↗
PubMed1976

Residual effects and skills related to driving after a single oral administration of diazepam, medazepam or lorazepam.

Psychomotor skills and visual functions related to driving were measured double-blind cross-over in ten healthy volunteers before, and 1,3,5 and 7 h after a single oral administration of diazepam (10mg), medazepam (15 mg) or lorazepam (2.5 mg). The late effects of lorazepam were tested in seven other subjects 12 and 24 h after the administration. Lorazepam impaired almost all the measured skills more (P less than 0.05 to 0.001) than diazepam, medizepam or the placebo. The lorazepam impairment of reactive skills and flicker fusion discrimination remained statistically significant (P less than 0.05) for as long as 12 h. Medazepam impaired only reactive skills and flicker fusion, the latter remaining impaired (P less than 0.05) for as long a 5 h after the administration. The magnitude and duration of the effects of diazepam were intermediate between those of lorazepam and medazepam. Diazepam impaired perceptual speed and reactive and co-ordinative skills as well as flicker fusion discrimination and visual parameters related to driving. Slight impairments in performance were measurable for up to 5 h after administration but at 7 h the results resembled those measured after the placebo. The lack of alterations in adaptation to darkness, sensitivity to brightness or visual discrimination ability in bright counterlight at a time when flicker fusion discrimination was severely depressed suggests that an impaired ability to discriminate flickering light is of no or little clinical significance to driving ability. It is concluded that patients receiving a 2.5 mg dose of lorazepam should not drive or operate machinery for 24 h after the administration. After diazepam (10 mg) or medazepam (15 mg) patients should refrain from driving or participating inskilled performances for only 5 to 7 hours.

Adult↗
PubMed1986

Effect of diazepam and medazepam on prolactin secretion.

Pharmacological studies of the effect of Diazepam and Medazepam on prolactin secretion were carried out on sexually mature male albino rats. The experiments were carried out using two series of experimental set-ups. In the first series an analysis was made of the effect of Diazepam in doses of 2 and 4 mg/kg body mass, and of Medazepam in doses of 1 and 10 mg/kg body mass, on the prolactin secretion on the 60th min after a single intraperitoneal injection. The second series of experiments was designed to investigate the effect of Diazepam and Medazepam in the same doses under conditions of acute immobilization of the animals for 60 min. The prolactin levels in the serum were tested using a radioimmunological method. Prolactin secretion decreases after a single intraperitoneal administration of Diazepam in both doses. Prolactin content in the serum was reduced only after a dose of 10 mg/kg body mass. Under conditions of experimental immobilization stress, prolactin secretion was stimulated in the animals from the control group, treated with standard solution used as solvent. Diazepam in both doses administered and Medazepam in a dose of 10 mg/kg inhibit the prolactin secretion stimulated by acute immobilization stress.

Animals↗
PubMed1982

A comparative study of the clinical effects of oral flunitrazepam, medazepam, and placebo.

In a double-blind randomized study 40 patients received 1 mg flunitrazepam, 40 patients received 10 mg medazepam, and 40 patients received placebo p.o. the night before surgery. On the morning of surgery each patient received another identical oral dose of the product or placebo taken the previous night. On the average, the flunitrazepam group slept better, was better sedated, and was less anxious than the medazepam or placebo groups. Similarly, as a reflection of diminished autonomic reactions, the patients receiving flunitrazepam had fewer cardiovascular changes. Flunitrazepam significantly decreased the amounts of thiopentone needed for induction of anesthesia. Medazepam did not. The pronounced sedative, sleep-inducing, and anxiolytic effects of flunitrazepam appear to be of great clinical importance for its use in anesthesiology. Repeated administrations of medazepam seem to be required to produce an evident clinical effect of the drug, possibly via the slow accumulation of metabolites. The main difference between these two benzodiazepine derivatives as regards clinical response therefore seems to be pharmacokinetic in origin.

Adult↗
PubMedDate not supplied

[The effects of medazepam on memory trace reproduction during learning and amnesia in aggressive and submissive C57Bl/6J mice].

Experiments were conducted on C57B1 mice to study the role of the social status on the reproduction of a conditioned reaction of passive avoidance and the effect of medazepam on the processes of reproduction. Aggressive and submissive animals were selected according to the test for agonistic confrontations. No effect of the animals' social status on the formation of a conditioned habit was revealed, but a significant increase in the level of defecation was recorded in the aggressive mice. Medazepam administration before the test reduced the reproduction of the conditioned reaction only in the control mice. An amnestic effect blocked reproduction in control and submissive mice but did not change it in the aggressors. Medazepam restored the amnestic memory trace only in submissive individuals. In aggressive mice it reduced the emotional response but did not change reproduction. The data obtained suggest that variations of the social status determine both the behavioral responsiveness to training and the changes in reproduction in response to medazepam.

Aggression↗
PubMed1976

Changes in excitability of amygdaloid and septal nuclei induced by medazepam hydrochloride.

Electrical stimulations of the central and basolateral part of the amygdaloid complex and of the septum in freely moving cats elicit changes in arterial pressure (i.e., an increase in pressure during stimulation of the central part of the amygdala, and a decrease followed by an increase during stimulation of the basolateral part of the amygdala and of the septum). These changes within the cardiovascular system are followed by rage reactions when the central part of the amygdala is stimulated, defense patterns when the basolateral part of the amygdala is stimulated, and pitiful mewing as a result of septal stimulation. Medazepam hydrochloride in a dose of approximately 15 mg/kg i.v. given over a period of 3 h, in order to maintain constant blood levels of the drug, attenuated slightly the cardiovascular reactions and elevated markedly the thresholds for psychomotoric behavior. The latencies between the onset of electrical stimulation and the beginning of the increase in arterial pressure were only slightly increased, whereas the latencies for spychomotoric behavior were markedly prolonged due to drug application. The data support the view that medazepam hydrochloride exerts depressant effects on the limbic-hypothalamic level with respect to psychomotoric responses. The effect was not identical for all nuclei tested. The basolateral part of the amygdala was significantly less sensitive to medazepam hydrochloride than the central part of the amygdala.

Amygdala↗
PubMed1987

Effects of medazepam on voltage-gated ion currents of cultured chick sensory neurons.

The effects of the benzodiazepine, medazepam, were investigated in current and voltage-clamped cultured chick dorsal root ganglion neurons. Under current clamp, micromolar concentrations initially elevated the action potential threshold and blocked both the sodium and calcium components of the spike. In voltage clamp, low (I(Ca.T)) and high (I(CA.N/L)) threshold calcium, sodium (I(Na)) and the delayed rectifier potassium (I(K)) currents were isolated by the use of appropriate solutions and voltage command protocols. Medazepam depressed both subtypes of I(Ca) equally well with calculated half-maximal depression at 77 microM. At a fixed concentration of 200 microM, medazepam depressed I(Na) (70 +/- 9%) and I(K) (73 +/- 6%) to a degree comparable to I(Ca) (75 +/- 3%). The results show that benzodiazepines can modulate the activity of several voltage-gated ion currents in chick dorsal root ganglion neurons.

Animals↗
PubMed1988

The effect of chronic diazepam and medazepam treatment on the number and affinity of muscarinic receptors in different rat brain structures.

1. The effect of chronic (19-day) treatment with the benzodiazepine tranquilizers diazepam (1 mg/kg/day, i.p.) and medazepam (5 mg/kg/day, i.p.) on the binding characteristics of muscarinic receptors in four rat brain structures: cerebral cortex, striatum, hippocampus and hypothalamus were studied using [3H]l-quinuclidinyl benzylate ([3H]QNB) as radioligand. 2. Diazepam and medazepam treatment caused an overall decrease in muscarinic receptor binding affinity (Kd). 3. The number (Bmax) of muscarinic receptors declined in the hippocampus and striatum and rose in the hypothalamus after both benzodiazepines. The Bmax of muscarinic receptors in the cerebral cortex was increased after diazepam treatment. 4. The changes in the binding characteristics of muscarinic receptors might be due to benzodiazepine-induced occurrence of two populations of muscarinic binding sites: P1 (high affinity, low capacity) and P2 (low affinity, high capacity). 5. The altered brain muscarinic receptor functions after chronic diazepam- or medazepam treatment suggest the role of cholinergic neurotransmission in the mechanism of action of benzodiazepines.

Animals↗
PubMed1988

A study of the induction of aneuploidy and chromosome aberrations after diazepam, medazepam, midazolam and bromazepam treatment.

Low passage-number cultured Chinese hamster cells were used to assess the ability of four benzodiazepines, namely diazepam, medazepam, midazolam and bromazepam, to induce numerical and structural chromosome aberrations. It was observed that diazepam, medazepam and midazolam treatment produced dose-dependent reductions in the number of diploid cells, with medazepam and midazolam inducing significant levels of hyperdiploidy and diazepam inducing low levels of hypodiploidy (at toxic doses). In contrast, bromazepam-treated cultures showed no significant changes in the level of aneuploidy even when exposed to toxic concentrations. All four sedatives were seen to induce low levels of chromosome aberrations, with bromazepam showing the most potent effect (albeit at a single toxic dose). These observations indicate that these structurally related benzodiazepines could be regarded as potentially genotoxic.

Aneuploidy↗
PubMed1990

Two kinds of spatiotemporal EEG changes after discontinuation of benzodiazepine, medazepam.

EEGs were recorded for Fp1, C3 and O1 once a week for 4 weeks after the withdrawal of medazepam, a benzodiazepine with a long half-life, from 7 normal males. Quantified analyses of them showed 2 types of change: A maximum change during the administration of medazepam that later tapered off. It consisted mainly of an increase in fast wave, and was uniform across areas though most significant in C3. A rebound phenomenon that reversed the change produced by the drug, the decrease in fast wave being significant in C3 during week 2. These results suggest that fast wave is the most sensitive EEG element and these 2 types of change must be investigated hereafter in terms of significant changes after the discontinuation of medazepam.

Adult↗
PubMed1990

Effect of diazepam and medazepam on pentylenetetrazol kindling in albino rats.

Experiments on male albino rats were carried out in order to study the effects of diazepam and medazepam on the clonic-tonic convulsions in kindling phenomena evoked by multiple injections of a subconvulsive dose (40 mg/kg) pentylenetetrazol (PTZ). In the two doses used, both diazepam (0.25 and 1.0 mg/kg) and medazepam (2.0 and 5.0 mg/kg) manifest a marked anticonvulsive effect on the clonic-tonic convulsions in PTZ-kindled rats, with a marked dose-effect dependence. The evidence in the literature that the hippocampus plays the role of a pathologically determining structure in the realization of the PTZ kindling and that neurotransmission in the inhibitory synapses in the hippocampus is achieved by gamma-aminobutyric acid (GABA), gives grounds to accept that the anticonvulsive effects of diazepam and medazepam, observed in PTZ kindling, occur through GABA-ergic mechanisms, because the facilitating effect of benzodiazepines on the GABA-ergic neurotransmission is well known.

Animals↗
PubMedDate not supplied

[Ethological analysis of the action of medazepam and diazepam on the zoosocial behavior of isolated mice].

Tests set up with isolated mice of two groups (aggressive and "fearful") evidenced that diazepam and medazepam weaken the behavioral manifestations of the partner's avoidance, increase sociability in "fearful" mice and help to regain the ability for elementary intraspecies contacts. These drugs have a biphasic action on the behavior of aggressive mice, small doses (medazepam 0.1 mg/kg) facilitating aggression and large one (medazepam, diazepam--5 mg/kg) suppressing it.

Aggression↗
PubMed1986

Effect of medazepam on benzodiazepine receptors in brain of mice with isolation syndrome.

The effect of medazepam in a model of isolation aggression in mice was studied according to Yen et al. It was established that the mean effective dose of medazepam was 250 micrograms/kg and the therapeutic index (LD50:ED50) 6200. The simultaneous biochemical investigations showed a reduction of the affinity and number of benzodiazepine receptors in the brain of aggressive animals. Medazepam 10 mg/kg p.o. led to the restoration of the number of benzodiazepine receptors at a single and 10-day treatment.

Aggression↗
PubMed1988

Effects of chronic diazepam and medazepam treatment on the level of biogenic monoamines in different rat brain areas.

Studies were made of the effect of 19-day administration of diazepam (1 mg.kg-1, i.p.) and medazepam (5 mg.kg-1, i.p.) on the level of biogenic monoamines in different rat brain areas: cerebral cortex, striatum, hippocampus, and hypothalamus. The noradrenaline (NA), dopamine (DA) and serotonin (5-HT) levels were determined. After chronic treatment with diazepam no alterations in the NA content in the cortex, striatum and hypothalamus were found. Medazepam increased the NA level in the cortex, striatum, and hippocampus without changing it in the hypothalamus. Repeated administration of diazepam or medazepam led to an increase in the DA level in the striatum. Both benzodiazepines provoked a significant increase in the hippocampal 5-HT level, which could be attributed to the antianxiety effect of these drugs.

Animals↗