UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of diazepam, clomipramine, and chlorpromazine upon cerebral metabolism and blood flow were examined separately in 18 dogs. After the administration of diazepam or clomipramine, cerebral cortical oxygen consumption (CMRO2) decreased significantly by a maximum of 17% and 13% of control within 10 minutes and 15 minutes, and returned to control at 120 minutes and 90 minutes, respectively. Chlorpromazine, however, decreased by a maximum of 10% of control, a level which continued throughout the period of observation. It was observed that reduction in CMRglucose was followed by the reduction in CMRO2 at an interval during the early stages of CMRO2 depression. Diazepam produced a significant decrease in CBF accompanied by reduction in CMRO2, but neither clomipramine nor chlorpromazine had any effect on CBF in spite of reduction in CMRO2. Reduction in CMRO2 both with diazepam and clomipramine was accompanied by slow wave activities of EEG, but with chlorpromazine reduction in CMRO2 was accompanied with less pronounced slow wave activities. It was concluded that the three drugs examined were cerebral metabolic depressants.
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PMID:Effects of psychotropic drugs on canine cerebral metabolism and circulation related to EEG--diazepam, clomipramine, and chlorpromazine. 118 21

Diazepam decreased the rate and amplitude of contraction in isolated embryonic chick hearts in a dose-dependent manner in both the noninnervated hearts obtained from 4-day-old embryos and the innervated hearts from 7-day-old embryos. The concentration of diazepam necessary to reduce the heart rate and contractile amplitude to 50% of the control values was about 1 X 10(-4) M. Concentrations less than 1.0 X 10(-5) M had no detectable depressant effects. Prior administration of atropine did not alter the depression induced by diazepam. Norepinephrine was able to stimulate the amplitude of contraction in the diazepam-depressed heart while atropine was without effect. The vehicle used in the clinical injectable preparation of diazepam had no depressant effects. The mechanism of action of the diazepam-induced depression on the isolated embryonic chick heart may be a direct depression of the myocardium.
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PMID:Effects of diazepam on the isolated chick embryo heart. 118 1

The effect of diazepam on soman-induced bradycardia and respiratory depression in rabbits has been investigated. Diazepam prevents the bradycardia produced by soman in conscious rabbits. Although atropine will reverse the respiratory depression produced by soman in anesthetized rabbits, diazepam enhances the depression and renders rabbits less susceptible to this action of atropine.
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PMID:Studies on the mechanism of the protective and antidotal actions of diazepam in organophosphate poisoning. 123 58

During a nine-month period we have treated 46 patients with status epilepticus with intravenous application of diazepam or midazolam. The initial doze od diazepam was 10 mg (rate: 2-5 mg/min) and of midazolam 15 mg (rate: 5 mg/min). Diazepam was effective in 26 and ineffective in 15 patients. Midazolam stopped status in 4 out of 7 patients. Both drugs were more effective when they were administered at the beginning of status. After the initial termination of status and recovering of consciousness, seizures returned in 10 patients (22%). In the group treated with diazepam, 4 patients had sudden apnea and 6 respiratory depression (totally 10 out of 41). In the group treated with midazolam, 3 had apnea and 2 respiratory depression (totally 5 out of 7). All patients with apnea or respiratory depression received higher doses of both drugs at the higher rates than the others. We conclude that the efficacy of the therapy is moderate while the frequency of serious complications is high. In status epilepticus, where the life of patient is in danger, drugs with such activity are of limited value.
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PMID:[Efficacy of therapy, recurrence of seizures and respiratory complications in the treatment of status epilepticus by intravenous administration of diazepam or midazolam]. 130 8

Benzodiazepines such as Valium (diazepam) or Versed (midazolam), as used in dental procedures for intravenous sedation, have been a boon to the profession. Yet in the event of sedation problems, no agent exists that consistently reverses all clinical effects of these drugs. This problem does not exist with narcotics, frequently employed in tandem with benzodiazepines, since an effective reversal agent, Narcan (naloxone hydrochloride), exists. It would be advantageous to effectively reverse benzodiazepines in cases of acute emergency with respiratory depression or paradoxical reactions, and to allow quick, full recovery after short dental procedures. None of the drugs currently available for benzodiazepine reversal, such as physostigmine, give consistent clinical results. The purpose of this paper is to discuss Flumazenil, a new specific benzodiazepine receptor antagonist, and its possible use for dental sedation procedures.
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PMID:Benzodiazepine reversal with flumazenil--a review of the literature. 135 May 1

Diazepam-sensitive (DS) and -resistant (DR) mice were selectively bred for increased and reduced sensitivity to the ataxic effects of diazepam (40 mg/kg). Other response differences between DS and DR mice may reflect pleiotropic effects of the genes fixed during their selection. These mice were tested for their sensitivity to the locomotor stimulant effects of several doses of diazepam, flunitrazepam, pentobarbital, phenobarbital, and ethanol. DR mice were more sensitive than DS mice to the locomotor stimulant effects of all drugs except phenobarbital. These results largely support the hypothesis that a common biological mechanism mediates sensitivity to the stimulant effects of sedative-hypnotic drugs. Receptor mediation of the benzodiazepine effects was examined by administering the benzodiazepine receptor antagonist, RO15-1788. Locomotor depression produced by diazepam and flunitrazepam in DS mice was blocked by RO15-1788. However, while the locomotor stimulation produced by diazepam in DR mice was antagonized, the stimulant effect of flunitrazepam was not. This suggests that binding of flunitrazepam to the GABAA-benzodiazepine receptor is not necessary for production of locomotor stimulation.
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PMID:Locomotor responses to benzodiazepines, barbiturates and ethanol in diazepam-sensitive (DS) and -resistant (DR) mice. 158 60

The intravenous anaesthetic agent propofol has become more and more popular not only for induction but also for the maintenance of anaesthesia in all fields of surgery. For this purpose, different infusion rates and also combinations of propofol with opioids, nitrous oxide and volatile anaesthetic agents have been described. The present study was designed to find the best dosage regimen for short operations and rapid changes. The necessity for the frequently recommended standardized combination of propofol with opioids should be checked with respect to the cardiovascular effects. METHODS. A series of 60 patients (ASA I and II, age range 22-79 years) selected for discectomy were prospectively randomized to three groups. Half an hour before operation all patient received 0.5 mg atropine, 50 mg promethazine and 50 mg pethidine as i.m. premedication. In all groups anaesthesia was induced with propofol in a bolus dose of 2.5 mg/kg body weight over a period of approximately 45 s. After 5 mg atracurium the patients were intubated under 100 mg succinylcholine and normoventilated with 70% nitrous oxide and 30% oxygen. For relaxation 25 mg of atracurium were given. In group I propofol was administered in a dosage of 15 mg/kg body weight per hour for 10 min after induction. After this time the propofol infusion was reduced to 6 mg/kg body weight per hour. Group II received 0.1 mg fentanyl before induction. The dosage of propofol was similar to group I. In group III 0.1 mg of fentanyl was administered before induction and propofol was given with an infusion rate of 6 mg/kg body weight from the beginning. The following parameters were controlled and documented: systolic and diastolic blood pressure (SAP and DAP), heart rate (HF), end-expiratory carbon dioxide (eeCO2), inspiratory oxygen concentration (FiO2) and peripheral oxygen saturation (sO2). Recovery time was determined as the time from the end of the propofol infusion until eye-opening on command. RESULTS. In all groups anaesthesia could be induced and maintained without complications. There was a slight increase in SAP in group I after intubation, while in the groups with fentanyl a pronounced decrease of SAP was found simultaneously with induction of anaesthesia (Fig. 1). In group I HF showed significantly higher values after intubation and for the next 15 min than in group II and group III. A rapid and pronounced increase of end-tidal carbon dioxide occurred in the fentanyl groups with the beginning of spontaneous ventilation at the end of anaesthesia. There was a significantly longer recovery time in group II with fentanyl and initial higher propofol infusion rate. A correlation between dosage of propofol and recovery time could not be found. DISCUSSION. The results of this study demonstrate that a routine combination of propofol with opioids is not necessary even for painful surgical procedures if the propofol dosage is initially increased. There are differences in cardiovascular reactions between group I without and groups II and III with fentanyl, but in our patients these changes were of no clinical importance. An additional administration of fentanyl can prevent hypertensive reactions or tachycardia with intubation, but on the other hand fentanyl can also increase the cardial depression of propofol with a dangerous decrease in blood pressure and heart rate. Therefore in combination with opioids lower doses of propofol should be used for induction and maintenance of anaesthesia. If opioids are administered, signs of a residual postoperative respiratory depression have to be taken seriously.
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PMID:[The use of propofol during diskectomy in neurosurgery]. 159 May 74

The mechanisms by which benzodiazepines produce muscle relaxation and respiratory depression are not known, but they may include actions on peripheral benzodiazepine receptors or central GABA receptors, or a direct action on airway smooth muscle may also be involved. We have compared, therefore, the effects of diazepam, flunitrazepam and midazolam on airway tone by measuring isometric tension of guineapig trachealis muscle. Cumulative concentrations of diazepam, flunitrazepam and midazolam caused concentration-dependent relaxation of resting tone in the tracheal smooth muscle with no significant differences in pD2 values (-log EC50--an index of potency) or intrinsic activities (% of maximum response) for relaxations for the three compounds. Pretreatment with propranolol 10(-6) mol litre-1, flumazenil 10(-7) and 10(-6) mol litre-1 or PK11195 10(-6) mol litre-1 had no effect on diazepam- or midazolam-induced relaxation. Diazepam 3 x 10(-6) mol litre-1 pretreatment shifted the concentration-response curves for acetylcholine, histamine and serotonin (5-HT) to the right by a factor of approximately 2. Flunitrazepam 3 x 10(-6) mol litre-1 pretreatment also shifted the curves for histamine and 5-HT similarly to the right, whereas midazolam pretreatment did not inhibit any agonist-induced contractions. These results suggest that benzodiazepines relax airway smooth muscle, not via neural pathways or central and peripheral benzodiazepine receptors, but by a direct action on airway smooth muscle.
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PMID:Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle. 163 6

Diazepam binding inhibitor (DBI) is a 9-kD polypeptide that was first isolated in 1983 from rat brain by monitoring its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the extracellular domain of the type A receptor for gamma-aminobutyric acid (GABAA receptor) and from the mitochondrial BZD receptor (MBR) located on the outer mitochondrial membrane. In brain, DBI and its two major processing products [DBI 33-50, or octadecaneuropeptide (ODN) and DBI 17-50, or triakontatetraneuropeptide (TTN)] are unevenly distributed in neurons, with the highest concentrations of DBI (10 to 50 microMs) being present in the hypothalamus, amygdala, cerebellum, and discrete areas of the thalamus, hippocampus, and cortex. DBI is also present in specialized glial cells (astroglia and Bergmann glia) and in peripheral tissues. In the periphery, the highest concentration of DBI occurs in cells of the zona glomerulosa and fasciculata of the adrenal cortex and in Leydig cells of the testis; interestingly, these are the same cell types in which MBRs are highly concentrated. Stimulation of MBRs by appropriate ligands (including DBI and TTN) facilitates cholesterol influx into mitochondria and the subsequent formation of pregnenolone, the parent molecule for endogenous steroid production; this facilitation occurs not only in peripheral steroidogenic tissues, but also in glial cells, the steroidogenic cells of the brain. Some of the steroids (pregnenolone sulfate, dehydroepiandrosterone sulfate, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 3 alpha, 21-dihydroxy-5 alpha-pregnan-20-one) produced in brain (neurosteroids) function as potent (with effects in the nanomolar concentration range) positive or negative allosteric modulators of GABAA receptor function. Thus, accumulating evidence suggests that the various neurobiological actions of DBI and its processing products may be attributable to the ability of these peptides either to bind to BZD recognition sites associated with GABAA receptors or to bind to glial cell MBRs and modulate the rate and quality of neurosteroidogenesis. The neurobiological effects of DBI and its processing products in physiological and pathological conditions (hepatic encephlopaty, depression, panic) concentrations may therefore be explained by interactions with different types of BZD recognition site. In addition, recent reports that DBI and some of its fragments inhibit (in nanomolar concentrations) glucose-induced insulin release from pancreatic islets and bind acyl-coenzyme A with high affinity support the hypothesis that DBI isa precursor of biologically active peptides with multiple actions in the brain and in peripheral tissues.
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PMID:Diazepam binding inhibitor (DBI): a peptide with multiple biological actions. 164 40

The influence of diazepam, an agonist, and flumazenil (Ro 15-1788), an antagonist of the benzodiazepine receptor, on repetitive firing of action potentials in cultured spinal neurons and on voltage-dependent Na+ currents in cultured N2A neuroblastoma cells was examined. The effects were compared to those of the antiepileptics phenytoin and carbamazepine and the local anesthetic lidocaine. The whole-cell configuration of the patch-clamp technique was used for potential and current recording. Diazepam (10 microM) or phenytoin (10 microM) reduced the duration of repetitive action potential discharges in 50 or 67% of the spinal neurons, respectively. At a concentration of 100 microM repetitive firing was completely blocked. Flumazenil (100 microM) had no effect. In N2A neuroblastoma cells diazepam, phenytoin, carbamazepine and lidocaine, but not flumazenil, at a concentration of 100 microM reduced the Na+ current to 60-67% of control. At 10 microM no or only a weak depression was seen with any drug. In the presence of diazepam (100 microM) the Na+ channel inactivation curve was shifted in the hyperpolarizing direction by -4.8 +/- 0.5 mV. Phenytoin, carbamazepine and lidocaine (all 100 microM) caused stronger shifts of -17.4 +/- 2.1, -10.6 +/- 0.9 and -17.0 +/- 2.1 mV, respectively. Inhibition of the Na+ current by diazepam increased use-dependently over 9 depolarizing pulses repeated at high frequency (200 Hz), whereas use-dependent effects of the other compounds developed less rapidly. At a low stimulation rate (7 Hz) use-dependent block was pronounced with lidocaine, but weak or absent with diazepam and carbamazepine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Action of diazepam on the voltage-dependent Na+ current. Comparison with the effects of phenytoin, carbamazepine, lidocaine and flumazenil. 165 Nov 46

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