Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIAZEPAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1990

Magnesium sulphate versus diazepam in the management of eclampsia: a randomized controlled trial.

This randomized controlled trial compared the use of magnesium sulphate with diazepam as anticonvulsant in 51 eclamptic women. The use of magnesium sulphate was associated with less serious morbidity (in terms of recurrence of convulsions, cardiopulmonary problems, disseminated intravascular coagulopathy, and acute renal failure) but the difference was not statistically significant (relative risk 0.6; 95% CI 0.3 to 1.2). The one maternal death occurred in the magnesium sulphate group. Convulsions recurred in five (21%) women in the magnesium sulphate group and seven (26%) women in the diazepam group. Urine output poor enough to prompt diuretic stimulation was less frequent in the magnesium sulphate group than in the diazepam group (RR 0.3; 95% CI 0.1 to 0.9). Significantly fewer infants born in the magnesium sulphate group had low Apgar scores (less than 7 at 1 min) compared with those in the diazepam group (RR 0.6; 95% CI 0.4 to 0.9). There were two early neonatal deaths in the magnesium sulphate group, and three stillbirths in the diazepam group. This study suggests that magnesium sulphate has advantages over diazepam for the mother and the infant in the treatment of eclampsia, but the trial is small and should be replicated on a larger scale.

Apgar Score↗
PubMed1995

Changes in benzodiazepine-GABA receptor coupling in an accumbens-habenula circuit after chronic diazepam treatment.

1. The effects of subacute and of chronic diazepam treatment upon binding to the GABAA receptor have been examined by use of receptor autoradiography for determining flunitrazepam (FNZP) binding, GABA enhancement of FNZP binding. SR 95531 2-(3'-carboxy-2',propyl)-3-amino-6-p-methoxyphenylpyridazinium bromide) binding and GABA binding in parallel sections from rat brain. Prior to the autoradiographic procedures, a behavioural assessment of the rats was made in the elevated plus-maze test of anxiety. 2. Rats receiving diazepam either subacutely (3 days) or chronically (28 days) by both continuous release, from previously implanted subcutaneous silastic capsules, or by daily injection (5 mg kg-1) did not display changes in FNZP or GABA binding in any of the 47 brain structures analysed. Similarly, there were no significant effects of treatment upon mean total entries or on the open:total ratio for entries in the elevated plus-maze. 3. There were reductions in the GABA enhancement of FNZP binding in the nucleus accumbens and central grey after subacute diazepam treatment. This effect persisted in the nucleus accumbens after chronic treatment. Less marked effects occurred in the lateral habenula, dorsal raphe and substantia nigra pars compacta. In the dorsal tegmental nucleus, GABA enhancement of FNZP binding was enhanced after chronic treatment and this was accompanied by reductions in SR 95531 binding. Treatment did not otherwise affect SR 95531 binding, with the exception of the dorsal raphe where binding was decreased after subacute treatment. 4. In general, the patterns of binding produced by the two different treatment routes were very similar. However, SR 95531 binding was lower in certain hippocampal fields in the i.p. treated animals compared to the rats implanted with silastic capsules. 5. It is concluded that repeated administration of diazepam evokes changes in benzodiazepine and GABA receptor coupling, and to a lesser extent changes in low affinity GABA binding, in certain interrelated brain structures of which an accumbens-habenula circuit is a central feature. These changes occur soon after the initiation of diazepam treatment, suggesting that they are unlikely to account for tolerance to the anxiolytic effects of diazepam but may trigger and/or accompany other critical neurochemical events.

Animals↗
PubMed1979

Antipyretic effect and plasma concentrations of rectal acetaminophen and diazepam in children.

Plasma levels of acetaminophen (paracetamol) and diazepam were measured in 9 children by gas chromatography after administering these drugs simultaneously in separate suppositories. The antipyretic effects of oral and rectal acetaminophen-diazepam combinations were also studied and compared with that of oral or rectal acetaminophen alone. Diazepam at a dose of 0.2 mg/kg did not increase the antipyretic action of acetaminophen. Acetaminophen and diazepam seemed to be well absorbed from the rectal suppositories, the maximal plasma concentration of diazepam after a rectal dose of 0.5 mg/kg just reaching the assumed anticonvulsant level in about 2 hr. In light of this study, an acetaminophen-diazepam combination in separate suppositories may be suitable for the prevention of recurrent febrile convulsions in susceptible children, but its practical value and efficacy require evaluation in clinical experiments.

Acetaminophen↗
PubMed1981

Effects of diazepam on hippocampal excitability in the rat: action in the dentate area.

Acute and chronic experiments were performed on rats to examine the effects of diazepam (Valium) on recurrent inhibition in the monosynaptic perforant path-dentate synapse of the dentate area of the dorsal hippocampus. Evidence was obtained which indicated that diazepam facilitated a presumably GABA mediated post synaptic recurrent inhibition in both acute and chronic preparations at 1 and 2 mg/kg doses (IP). Acute studies also revealed that diazepam prolonged recurrent inhibition, possibly by lengthening the IPSP. An effect of the drug on cholinergically mediated positive feedback from the septum could not be ruled out, however. Taken together, this study extends the evidence that diazepam acts centrally on GABA mediated inhibition in the limbic system. Furthermore, the limbic action of diazepam revealed here suggests a mechanism for the anticonvulsant properties of diazepam in epilepsy involving subcortical (limbic) circuitry.

Animals↗
PubMed1982

Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats.

The 1.5-benzodiazepine (clobazam), the 1,4-benzodiazepine (diazepam), and two nonbenzodiazepine antiepileptic drugs (phenobarbital and valproate) were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that clobazam and valproate exhibit a wider range of experimental anticonvulsant activity than either diazepam or phenobarbital. Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine). Clobazam is effective by the MES test in rats only in doses that exceed the median minimal toxic dose. Phenobarbital is effective against all of the above tests, but minimal toxic doses must be employed to prevent strychnine seizures. Diazepam, on the other hand, is effective in nontoxic doses against seizures induced by Metrazol, bicuculline, and picrotoxin, but protects animals from maximal electroshock and strychnine seizures only when given in toxic doses. When compared on the basis of protective indices (PI = TD50/ED50) calculated from intraperitoneal data, the PIs for clobazam were 1.6 to 13 times higher than those for diazepam. Overall, except for the MES test in rats, the PIs for clobazam were from 1.5 to 44 times higher than those for any of the other three substances. With respect to the MES test in rats, the PI for clobazam was 10.8 times higher than that for diazepam; however, the PIs for phenobarbital and valproate were 3.5 and 4.4 times higher, respectively, than that for clobazam. These data suggest that the spectrum of anticonvulsant activity for the 1,5-benzodiazepine (clobazam) is superior to that for the 1,4-benzodiazepine (diazepam). Also, the broad experimental profile of anticonvulsant activity of clobazam agrees well with its reported broad clinical efficacy.

Animals↗
PubMed1982

Absorption of diazepam from the rectum and its effect on interictal spikes in the EEG.

Rectal administration of several different preparations of diazepam to a group of adult volunteer patients with epilepsy produced variable rates of absorption. Peak serum concentrations following 10 mg, 20 mg, and 30 mg of diazepam solution were achieved between 13-60 min, 10-120 min, and 30-90 min respectively. An experimental diazepam "solid solution" suppository was found to have significantly better absorption characteristics compared with the commercially available Valium suppository. Diazepam solution 20 mg was administered rectally in 10 adult epileptic patients with frequent spontaneous interictal spikes in their EEGs. A highly significant reduction in spike frequency was seen compared with placebo. The effect was most marked 10-20 min after administration of diazepam, when the mean spike count fell to 39 +/- 35 SD percent of the control value (p less than 0.01), and this corresponded with a mean serum diazepam level of 210 +2- 125 ng/ml.

Adolescent↗
PubMed1996

Effect of diazepam on plasma gamma-aminobutyric acid in sons of alcoholic fathers.

A subgroup of abstinent alcoholics, display low levels of plasma gamma-aminobutyric acid (GABA). Two previous studies of plasma GABA in sons of alcoholic fathers (SOAs) have yielded conflicting results. The aim of the current study was to measure plasma GABA both at baseline and after challenge with diazepam, a GABAA receptor agonist, in a group of SOAs already shown to display decreased eye movement, memory, and sedative effects of diazepam. Twenty-seven SOAs and 23 male control subjects received four logarithmically increasing doses of diazepam or placebo in randomized order on 2 days at least 1 week apart. Plasma GABA was measured at baseline and after the last dose. There were no significant differences between SOAs and controls in baseline plasma GABA levels. In the whole sample, there were significant correlations between baseline plasma GABA and both high novelty-seeking and low-harm avoidance scores on the Tridimensional Personality Questionnaire. Both SOAs and controls displayed decreases in plasma GABA over time on both testing days, but there was no effect of diazepam on plasma GABA and no significant difference between groups in plasma GABA response to diazepam. These results suggest that neither low plasma GABA at baseline nor altered plasma GABA response to diazepam is associated with increased genetic risk for alcoholism.

Adolescent↗
PubMed1978

Delirium tremens: a double-blind comparison of diazepam and barbital treatment.

The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a "special purpose drug" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens.

Administration, Oral↗
PubMed1977

Unchanged protein binding and the increase of serum diazepam levels after food intake.

Seven subjects received diazepam 0.3 mg/kg intravenously twice with a 2-week interval between the doses. The subjects ingested a fatty or carbohydrate meal in a cross-over fashion 4 hours after the injection on both experimental days. Venous blood samples were drawn 2, 3, 4, 5 and 6 hours after the injection of diazepam for measurement of the serum levels of total and free (unbound) diazepam, N-desmethyldiazepam, and free fatty acids. Serum levels of diazepam decreased progressively with time until the food intake, after which a significant (P less than 0.01) postprandial increase (average 23%) occurred with both diets as compared to the preprandial levels at 4 hours (average 240 ng/ml). Serum levels of free fatty acids decreased significantly both after a fatty (P less than 0.01) and a carbohydrate (P less than 0.05) meal. Diazepam was extensively (96 to 98%) bound to proteins and no changes in its protein binding was found. It is concluded that the late impairment of psychomotor skills that occurs with an increase in the diazepam serum level after its intravenous administration is due rather to its re-mobilization from a storage site than to variations in its protein binding.

Adult↗
PubMed1999

Diazepam inhibits forskolin-stimulated adenylyl cyclase activity in human tumour cells.

Previous studies have shown that the benzodiazepine agonist, diazepam, suppresses adenylyl cyclase activity in rat brain, via a G protein-coupled benzodiazepine receptor. Since diazepam binding sites are also present in diverse non-neuronal tissues including tumour cells, its effects on adenylyl cyclase activity were examined in membranes from human MCF-7 (breast cancer) and M-6 (melanoma) cells. Diazepam caused a biphasic and concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase activity in MCF-7 membranes. The first phase of inhibition, at picomolar to nanomolar drug concentrations (EC50=5.7 x 10(-12)M), is similar to the receptor mediated phase observed in the rat brain. At micromolar concentrations of diazepam (EC50= 1.8 x 10(-4)M), the steep decrease in adenylyl cyclase activity may involve a direct action on the enzyme itself, as detected previously in rat brain membranes. Diazepam-induced suppression of adenylyl cyclase activity was also detected in M-6 membranes. However, in contrast to MCF-7 findings, only micromolar concentrations of diazepam (EC50=5.2 x 10(-4)M) inhibited enzyme activity in M-6 membranes. These findings suggest that G protein-coupled benzodiazepine receptors, which mediate inhibition of the adenylyl cyclase-cAMP pathway in the brain, are also expressed in MCF-7 cells.

Adenylyl Cyclase Inhibitors↗
PubMed1993

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans.

Effects of the GABAergic drug diazepam (0.15 mg kg-1, i.v.) on cardiovascular and endocrine responses to 50 degrees head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1,10) = 6.45; P < 0.03). After 42 +/- 4 min of sustained tilt with saline (control) and 47 +/- 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2-3-fold increase in plasma ACTH, beta-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.

Adult↗
PubMed1990

Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone, diazepam and zolpidem in unstressed rats.

This study has compared the effects of a cyclopyrrolone, zopiclone, a benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal cortex. The endogenous levels of DA were significantly increased by both zopiclone (2.5, 10 and 40 mg kg-1 p.o.) and diazepam (10 and 40 mg kg-1 p.o.) in the prefrontal cortex, whereas striatal DA content was significantly increased only with the highest dose of diazepam (40 mg kg-1 p.o.). Diazepam (10 and 40 mg kg-1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels, whereas zopiclone (40 mg kg-1 p.o.) only slightly decreased striatal DOPAC levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an effect which was more marked in prefrontal cortex than in striatum. This result was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most potent at decreasing DA utilization at the cortical level. The diazepam-induced decreases in DA metabolism and utilization were antagonized by Ro 15-1788, suggesting that the effects seen were mediated by specific benzodiazepine receptors. Thus, our results clearly show that ligands acting on the benzodiazepine receptor GABA receptor chloride ionophore complex can decrease the utilization of dopamine in unstressed rats. The preferential decrease in cortical DA utilization induced by benzodiazepine ligands may be compared to the well-known activation by stress of the mesocortical DAergic system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Efficacy and the discriminative stimulus effects of negative GABAA modulators, or inverse agonists, in diazepam-treated rhesus monkeys.

In benzodiazepine (BZ)-dependent animals, the effects of negative GABA(A) modulators at BZ sites are not clearly related to differences in negative efficacy (i.e., inverse agonist activity). A flumazenil discriminative stimulus in diazepam (5.6 mg/kg/day)-treated rhesus monkeys was used to test the hypothesis that the effects of negative GABA(A) modulators at BZ sites do not vary as a function of efficacy in BZ-dependent animals. Negative GABA(A) modulators varying in efficacy were studied in combination with positive modulators acting at different modulatory sites (BZ, barbiturate, and neuroactive steroid sites). The negative modulators Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]benzodiazepine-3-carboxylate) and ethyl beta-carboline-3-carboxylate (beta-CCE) substituted for the flumazenil discriminative stimulus. Acute pretreatment with diazepam (3.2 and 10 mg/kg s.c., in addition to 5.6 mg/kg/day p.o.), pentobarbital (3.2 and 10 mg/kg), or pregnanolone (1 and 3.2 mg/kg) attenuated the flumazenil discriminative stimulus and also attenuated the flumazenil-like discriminative stimulus effects of Ro 15-4513 and beta-CCE. Attenuation of the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE did not systematically vary as a function of negative efficacy. Compared with their discriminative stimulus effects in untreated monkeys discriminating midazolam, both pregnanolone and pentobarbital were relatively more potent than diazepam in attenuating the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE in diazepam-treated monkeys. These results show that the discriminative stimulus effects of BZ-site neutral and negative modulators are not different in BZ-dependent animals trained to discriminate flumazenil, and extend the results of a previous study showing that positive modulators acting at non-BZ sites are especially potent in attenuating the effects of flumazenil in diazepam-treated monkeys (i.e., diazepam withdrawal).

Animals↗
PubMed1979

Rectal administration of diazepam in solution in the acute treatment of convulsions in infants and children.

In a prospective study 44 children, aged 6 months to 5 years, admitted to hospital with febrile convulsions or epilepsy, were treated with diazepam in solution administered rectally during 59 generalised attacks. Rectal administration of diazepam was effective in the acute treatment of convulsions in 80% of cases. In 10% the treatment failed, whereas diazepam administered intravenously had prompt effect; another 10% of the convulsions wer resistant to diazepam, irrespective of the route of administration. The therapeutic effect was significantly correlated with the duration of convulsions before treatment started. Early treatment (convulsions less than or equal to 15 minutes) had effect in 96%, and late treatment (convulsions greater than 15 minutes) in 57% of cases. A total of 317 children admitted with febrile convulsions were treated prophylactically with diazepam administered rectally whenever the temperature was greater than or equal to 38.5 degrees C. No case of significant respiratory depression or other serious side effects was observed. The rapid and reliable anticonvulsant effect of diazepam given rectally and the very few side effects makes this treatment a valuable alternative to IV administration in childhood.

Acute Disease↗
PubMed1981

Drug treatment of breathlessness: contrasting effects of diazepam and promethazine in pink puffers.

Fifteen out of 18 "pink and puffing" patients completed a double-blind, placebo-controlled cross-over trial of diazepam and promethazine for breathlessness and reduced exercise tolerance. Dosages were 25 mg and 125 mg daily, respectively, and each course lasted two weeks. Patients with psychiatric or other major medical histories were excluded. Of the three patients who did not complete the trial, one died during an exacerbation of breathlessness while taking diazepam, one was withdrawn because of mild hypercapnia while taking placebo, and one suffered intolerable drowsiness while taking diazepam. Of the remaining 15 patients, six needed a reduction in dosage because of drowsiness: one of these was taking promethazine and five diazepam. Diazepam had no effect on breathlessness and noticeably reduced exercise tolerance. Promethazine reduced breathlessness and improved exercise tolerance without altering lung function. From these results diazepam is contraindicated for breathlessness and reduced exercise tolerance in fixed airways obstruction, but promethazine may be beneficial.

Adult↗
PubMed1970

Value of diazepam ('Valium') in treatment of cardiac arrhythmias.

Diazepam did not alter the rate or rhythm in III patients with atrial fibrillation. In 3 out of 38 patients with atrial flutter the use of diazepam was followed by an increase in atrioventricular block. Diazepam restored sinus rhythm in I patient with atrial tachycardia (total 7 patients) and in I patient with ventricular tachycardia (total 8 patients). Experimentally in the dog diazepam raised the electrically-induced ventricular tachycardia threshold significantly. Pretreatment with diazepam did not alter significantly the dose of strophanthidin K required to induce ventricular tachycardia in the dog. The value of diazepam as a cardiac anti-arrhythmic agent should be further assessed in a controlled clinical trial, especially in patients with acute myocardial infarction.

Aged↗
PubMed1984

A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients.

The clinical anticonvulsant efficacy of single dose rectal and oral administration of diazepam 20 mg was examined in two double-blind placebo-controlled trials in adult epileptic patients. All subjects suffered from drug resistant epilepsy and frequently experienced serial seizures. Diazepam was administered rectally as a new experimental suppository formulation immediately after a seizure and was highly effective in preventing recurrent fits within a 24 h observation period (p less than 0.001). Pharmacokinetic studies revealed a wide range of serum diazepam concentrations 60 min after administration of the suppository (mean serum diazepam level 190 +/- 73 (SD ng/ml). In a similar study oral administration of diazepam 20 mg significantly reduced the incidence of serial seizures compared with a placebo (p less than 0.01) and the mean 60 min serum diazepam level was 273 +/- 190 (SD) ng/ml.

Administration, Oral↗
PubMed1982

The effect of diazepam on adenosine uptake and adenosine-stimulated adenylate cyclase in guinea-pig brain.

We have used the adenosine-stimulated adenylate cyclase of guinea-pig brain to examine the potency of diazepam as an adenosine uptake inhibitor. Diazepam at concentrations in the range 10--500 microM stimulates the production of cAMP in incubated slices of guinea-pig cerebral cortex, with maximal fivefold stimulations over basal levels by 200 microM diazepam. The increases can be largely (but not completely) blocked by the adenosine antagonist theophylline or by addition of excess adenosine deaminase to the system. It appears that the stimulation of cAMP production is due to a blockade of adenosine uptake which results in an increase in extracellular adenosine and concomitant activation of the adenosine receptor coupled to adenylate cyclase. Since the cAMP response to standard adenosine uptake blockers (dipyridamole, dilazep) can be completely blocked by theophylline or adenosine deaminase, a small component of the diazepam response cannot be explained by an adenosine effect. The concentration of diazepam at which the first significant cAMP increase occurs is 10 microM or slightly lower. This is significantly higher than the concentration of diazepam needed to saturate the pharmacologically characterized central nervous system receptors for benzodiazepines.

Adenosine↗