Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Midazolam in combination with nitrous oxide (N2O) is a commonly used sedative approach for pediatric dental patients. Respiratory morbidity and mortality have been reported with midazolam administration, particularly when used in combination with other drugs in the absence of supplemental oxygen. Thus, the purpose of this investigation was to determine the effect of midazolam alone and in combination with N2O on respiration in laboratory rats by measuring arterial blood gas levels. Sixty-four Sprague-Dawley rats, weighing 250-320 g, were assigned to one of eight groups (eight per group). Groups were allocated based upon the dosage of midazolam administered (0, 1.0, 2.0 or 4.0 mg/kg i.p.) and exposure to N2O/02 (50%/50%) or room air. Arterial blood was obtained from a femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were determined. Samples were analyzed using a System 1306 pH/Blood Gas Analyzer. Baseline arterial blood gasses were obtained for each animal and at 15-min intervals following midazolam administration throughout the 45-min experiment. Following midazolam administration, animals were placed into a sealed chamber through which flowed either N2O or room air. Group comparisons demonstrated that: 1) arterial CO2 levels increased in midazolam-exposed animals breathing room air, but not in those exposed to N2O (P < 0.05), and 2) as expected, N2O/O2-exposed animals showed an increase in arterial O2 and a %saturation that was not observed in room air groups (P < 0.01). This investigation demonstrated that coadministration of N2O/O to midazolam-exposed animals did not result in hypercarbia, an early indicator of respiratory depression.
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PMID:The influence of midazolam and nitrous oxide on respiratory depression in laboratory rats. 885 55

Benzodiazepines, which may themselves have analgesic properties, display complex interactions with opioids. This study was designed to investigate the effects of midazolam on nociceptive neurotransmission in isolated neonatal rat spinal cord, and the interactions between midazolam and alfentanil. Slow ventral root potentials (sVRP) were recorded from a lumbar root of spinal cords isolated from 1-7-day-old rats and superfused at 27-28 degrees C. Midazolam (35 nmol litre-1 to 15 mumol litre-1) significantly (P < 0.05) depressed sVRP area in a concentration-dependent manner. Midazolam depression was antagonized by flumazenil, bicuculline and naloxone. Midazolam and alfentanil interacted synergistically, as determined by a combination index of less than 1. Midazolam blocked the rebound hyperexcitability observed when alfentanil was reversed by naloxone. The results of the study are relevant to benzodiazepine-opioid analgesia and to the effectiveness of benzodiazepines in mitigating the development of opioid tolerance and dependence.
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PMID:Synergistic interactions between midazolam and alfentanil in isolated neonatal rat spinal cord. 894 14

Midazolam is a familiar agent commonly used in the emergency department to provide sedation prior to procedures such as laceration repair and reduction of dislocations. Midazolam is also effective in the treatment of generalized seizures, status epilepticus, and behavioral emergencies, particularly when intravenous access is not available. Midazolam is often employed as an induction agent for rapid sequence endotracheal intubation. Midazolam has a rapid onset of action following intravenous, intramuscular, oral, nasal, and rectal administration. Only 50% of an orally administered dose reaches the systemic circulation due to extensive first-pass metabolism. Midazolam is metabolized by the cytochrome P450 enzyme system to several metabolites including an active metabolite, alpha-hydroxymidazolam. Cytochrome P450 inhibitors such as cimetidine can profoundly reduce the metabolism of midazolam. Midazolam has a half-life of approximately 1 h, but this half-life may be prolonged in patients with renal or hepatic dysfunction. Midazolam has been associated with respiratory depression and cardiac arrest when used in combination with an opioid, particularly in the elderly, although all ages are at risk for respiratory depression. Midazolam is relatively free of side effects when used alone and offers several advantages over traditional pharmacological agents such as chloral hydrate and the combination of meperidine, chlorpromazine, and promethazine. Hiccups, cough, nausea, and vomiting are the most commonly reported adverse effects. Many of the adverse effects associated with midazolam can be reversed rapidly by the administration of flumazenil, a competitive benzodiazepine receptor antagonist. Midazolam is a safe and effective agent for providing sedation in the emergency department.
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PMID:Midazolam: a review of therapeutic uses and toxicity. 925 87

We investigated whether adenosine neuromodulation is involved in a benzodiazepine (midazolam)-induced depression of excitatory synaptic transmissions in the CA1 and dentate gyrus (DG) regions in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs), evoked by electrical stimulation of the CA1-Schaffer collateral or the DG-perforant path, were recorded with extracellular microelectrodes from CA1-stratum radiatum or DG-stratum moleculare in oxygenated ACSF. The initial slope of the fEPSPs was analyzed for assessing the drug effects. Midazolam (1 microM) transiently depressed CA1- and DG-fEPSPs. The fEPSPs were depressed to approximately 75% of the control values, and then gradually recovered. The depression was not affected by bicuculline, a GABAA receptor antagonist, although it was completely antagonized by aminophylline, an adenosine receptor antagonist. Dipyridamole (5 microM), an adenosine uptake inhibitor, depressed the fEPSPs in a similar manner to midazolam. An adenosine deaminase inhibitor, EHNA, also transiently depressed the fEPSPs, but in a different manner. Exogenous adenosine persistently depressed the fEPSPs. The effects of the drugs were not significantly different in the CA1 and DG regions. The results suggest that midazolam (1 microM) depresses excitatory synaptic transmissions through the adenosine neuromodulatory system by inhibiting adenosine uptake in the CA1 and DG regions of the hippocampus.
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PMID:Involvement of the adenosine neuromodulatory system in the benzodiazepine-induced depression of excitatory synaptic transmissions in rat hippocampal neurons in vitro. 1009 72

Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
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PMID:Midazolams cardiac depressant effects and their lack of reversal by flumazenil in isolated rabbit hearts. 1020 58

Generalized convulsive status epilepticus (GCSE) is a medical emergency requiring prompt resolution. Acute treatment is often delayed by difficulty in obtaining intravenous (i.v.) access. Refractory GCSE is often difficult to treat, and traditional therapy with barbiturates induces hypotension and respiratory depression and prolongs recovery. Midazolam is particularly useful for treating acute GCSE because it has an imidazole ring that is open at low pH, allowing it to be dissolved in aqueous solution for intramuscular injection, but closed at physiologic pH, increasing lipophilicity and rendering good intramuscular absorption, brain penetration, and fast onset of action. When given intramuscularly as a 0.2 mg/kg bolus, it has efficacy at least equal to that of i.v. diazepam, is well tolerated, induces little respiratory compromise, and has a shorter latency to onset of action. Therefore, it should be considered for the treatment of acute GCSE when i.v. access is problematic. For refractory GCSE, continuous i.v. midazolam infusion at 0.1-0.6 mg/kg/hr after a 0.2 mg/kg i.v. bolus is effective and has advantages over traditional therapies because it induces less hypotension and cardiorespiratory depression and can be easily titrated. Further prospective studies are needed to define the role of continuous i.v. midazolam compared to other contemporary therapies.
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PMID:Midazolam treatment of acute and refractory status epilepticus. 1051 75

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.
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PMID:Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points. 1092 12

Some of anesthetic drugs cause cardiac arrhythmia, myocardial depression, blood pressure as well as hepatic and renal blood flow decrease. The aim of the following research study was the evaluation of midazolam effect on hemodynamic parameters in propranolol-treated rabbits. The following parameters: cardiac output and stroke volume, peripheral blood resistance, heart rate and blood pressure were estimated in the hemodynamics study. Blood pressure was significantly higher in case of propranolol and midazolam therapy as compared with midazolam alone. Blood pressure inconstancy did not exceed 20% of the initial value. Midazolam did not improve the depressive effect of propranolol on heart rate. The peripheral vascular resistance in coherent propranolol and midazolam therapy oscillated at the values observed after sole midazolam administration. After midazolam administration with propranolol, insignificant increase of cardiac output and stroke volume during the first minutes of experimental protocol correlated with marked decrease of peripheral blood resistance at the same time.
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PMID:Effect of propranolol and midazolam therapy on hemodynamic parameters in rabbits. 1120 29

The aim of this study was to elucidate the effects of midazolam and ketamine on neuromuscular blockade induced by non-depolarizing muscle relaxants (NDMRs) under the condition of sepsis induced by panperitonitis. A CLP operation (laparotomy, cecal ligation, and puncture of the cecum; septic group) or sham laparotomy (sham group) was performed on rats under O2-isoflurane anesthesia. At 18 hours after the operation, isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect or direct stimulation at 0.1 Hz were measured. Midazolam enhanced the dTc (1 microM)-induced twitch depression (p < 0.05) at a high concentration (10 microM) in the septic group but not in the sham group. Ketamine enhanced the dTc (1 microM)-induced twitch depression in the sham group (p < 0.01) but not in the septic group. Midazolam and ketamine had no effect on directly elicited twitch tensions in either group. The results indicate that sepsis facilitates the midazolam-induced enhancement of the neuromuscular blocking effect of dTc but, conversely, inhibits the ketamine-induced enhancement. Sepsis elicits manifold alterations in the influence of intravenous anesthetics and sedatives on NDMR-induced neuromuscular blockade.
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PMID:The effects of midazolam and ketamine on D-tubocurarine-induced twitch depression in septic rat diaphragm. 1195 90

delta-Opioid receptor agonists have antidepressant-like effects in behavioral models of depression. Chronic administration of classical antidepressants upregulates mRNA expression of brain-derived neurotrophic factor (BDNF) and its high-affinity tyrosine kinase receptor, TrkB in the frontal cortex and hippocampus of rats. Increases in BDNF and TrkB levels are thought to be important for the therapeutic effects of these drugs. Therefore, we examined the ability of the delta-opioid receptor agonist (+)BW373U86 to regulate BDNF and TrkB mRNA expression in frontal cortex, hippocampus, as well as, basolateral amygdala, endopiriform nucleus, and primary olfactory cortex. At 3 h after a single administration of (+)BW373U86 animals were killed and BDNF and TrkB mRNA levels were examined by in situ hybridization. BDNF mRNA levels produced by (+)BW373U86 were compared to acute administration of the antidepressants desipramine and bupropion. A behaviorally antidepressant dose of 10 mg/kg (+)BW373U86 increased BDNF mRNA expression in all regions examined; a smaller dose of (+)BW373U86 (1 mg/kg) significantly increased BDNF mRNA expression only in frontal cortex. The delta-opioid receptor antagonist naltrindole blocked (+)BW373U86-mediated increases in BDNF mRNA expression. In addition, tolerance developed to increased BDNF mRNA expression with repeated injection, except in frontal cortex. Midazolam was administered to some animals to prevent the convulsions produced by (+)BW373U86, but midazolam did not block delta-opioid receptor-mediated increases in BDNF mRNA expression in frontal cortex, hippocampus, or amygdala. Unlike desipramine and bupropion, (+)BW373U86 upregulated BDNF mRNA expression acutely (within 3 h after a single administration). These data support the concept that delta-opioid receptor agonists may have antidepressant potential, and could be good targets for the development of faster-acting antidepressants.
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PMID:The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in rats. 1464 82


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