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)

A derivative of the 1,4-benzodiazepine series with reported opioid activity was evaluated in regard to its effect on central nervous activity in the awake canine. Additionally a possible benzodiazepine- or opioid-receptor interaction was evaluated by using specific antagonists. In 10 experiments increasing doses of tifluadom (5, 10, 20, 40, 80 micrograms/kg) modified somato-sensory-evoked potentials (SEP) inducing a dose-related latency change (40-80 micrograms/kg) and a suppression (80 micrograms/kg) of the P50-peak. Both effects are interpreted as a modification of stimuli reaching the somatosensory cortex. EEG-spectral analysis was characterized by a dose-related decrease of power in the higher frequency range (13-40 Hz) accompanied by an increase of power in the lower band (0.5-3.5 Hz). This effect was paralleled by deep sedation. The specific benzodiazepine antagonist Ro 15-1788 (240 micrograms/kg) was ineffective in reversing central nervous EEG- and SEP-changes. Naloxone (20 micrograms/kg) induced a short-term (5 min) arousal and a partial reversal of SEP-changes. The specific opioid-kappa-antagonist Mr 2266 (20 micrograms/kg) however, induced a long lasting return of power spectra and SEP-changes back to control. This results suggest that tifluadom, although being structurally a benzodiazepine, interacts with an opioid sub-receptor of the kappa-type, which is known to induce sedation and supraspinal analgesia without respiratory depression.
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PMID:[Tifluadom, a benzodiazepine with opioid-like activity: study of its central mechanism of action in conscious dogs]. 308 1

In 42 patients undergoing major surgery, anaesthesia was induced by intravenous alfentanil 10 micrograms/kg together with methohexitone 1.5 mg/kg or propofol 2 mg/kg. An infusion of six times these doses per hour was then started; the rate was varied subsequently as indicated by the monitoring of arterial blood pressure, heart rate, EEG and frontalis electromyogram. The mean duration of infusion was 76.7 minutes for propofol and 74.5 minutes for methohexitone and the infusion was stopped about 10 minutes before the end of surgery in each group. The induction dose differed, but the total dose requirement for the two drugs was similar. In every case, anaesthesia was satisfactory. Methohexitone caused a significant rise in mean pulse rate throughout anaesthesia (p less than 0.05, paired t-test). There was no change in mean pulse rate during propofol infusion. The dose of alfentanil used provided excellent control of autonomic reflexes, with negligible respiratory depression. Naloxone was not required. Propofol provided better anaesthesia than methohexitone, with fewer side effects (p less than 0.05, Chi squared test), easier control of the level of narcosis and faster recovery (p less than 0.001, t-test after log transformation).
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PMID:Propofol and alfentanil infusion. A comparison with methohexitone and alfentanil for major surgery. 308 51

In unanesthetized dogs prepared with chronic tracheostomies and chronically implanted intrathecal (IT) catheters having openings in the cisterna magna and lumbar region, lumbar IT injection of D-Ala2-D-Leu5-enkephalin (DADL, 1-10 mg) and morphine (3-30 mg) produced a dose-dependent depression of the slope of the CO2 response function (minute expired volume [VE] vs. end-tidal [ET] CO2) as investigated by a modified Read rebreathing technique. The maximum depression occurred less than 3 h after IT injection of either agent and lasted as long as 12 h. The depression was totally reversed by naloxone (0.4 mg/kg, iv). Naloxone alone had no effect on ventilatory function. After 10 mg DADL, there was no significant change in heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), cardiac output (CO), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), or PaO2 during the 3 h postinjection. In contrast, PaCO2 was significantly elevated and pH significantly decreased (P less than 0.05). Naloxone administration after high-dose IT DADL resulted in a doubling of MABP, MPBP, CO, and SVR that lasted approximately 20 min. In concurrently measured cisternal cerebrospinal fluid (CSF) levels, both morphine and DADL displayed peak levels by 30-60 min. The lumbar CSF clearance curves for both agents were fitted with a two-compartment intravenous bolus model. The t 1/2 alpha was 13.8 +/- 3.6 min for DADL and 9.4 +/- 1.6 min for morphine (mean +/- SE). The t 1/2 beta was 101.3 +/- 17.7 min for DADL and 116.7 +/- 27.9 min for morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiorespiratory effects and kinetics of intrathecally injected D-Ala2-D-Leu5-enkephalin and morphine in unanesthetized dogs. 309 39

We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systemically) at maximal effect of D-Ala-D-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or VT/TTOT decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on VT/TTOT and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE decreases heart rate by increasing parasympathetic activity to the heart and induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either direct opioid action on central respiratory regulation or parasympathetic non-muscarinic or non-cholinergic mediating mechanisms.
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PMID:Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids. 310 83

This paper reviews the use of prototypic drugs for reversal of the effects produced by anesthetic and sedative agents. Efficacy and toxicity information is presented for naloxone (as used to reverse opioids), physostigmine (as used for reversal of sedatives), and Flumazenil (a new specific benzodiazepine receptor antagonist). Naloxone is very useful and specific for reversing adverse and life-threatening respiratory depression caused by narcotic drugs and should be used in these situations. Physostigmime has been advocated in incremental doses for reversing sedative effects in patients who are obtunded or depressed after having received benzodiazepines, droperidol, scopolamine, opioids, and phenothiazines. Flumazenil has been shown to readily antagonize the sedative, respiratory depressant, anxiolytic, muscle relaxant, anticonvulsant, amnestic, and anesthetic effects of the benzodiazepines; it appears to have tremendous potential for use in anesthesia, conscious sedation, and emergency medicine when available.
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PMID:Reversal agents in sedation and anesthesia: a review. 313 41

The effects of ethanol ingestion and subsequent intravenously administered naloxone on the ventilatory response to hypercapnic hypoxia in 8 normal males and 8 normal females were examined. The responses of controls were lower in the females (-0.63 +/- 0.07 L/min/% SaO2) than the males (-1.11 +/- 0.18 L/min/% SaO2). Alcohol depressed the male response to a mean of -0.50 +/- 0.08 L/min/%SaO2 (p less than 0.01) but increased the mean female response to -0.87 +/- 0.11 L/min/%SaO2 (p less than 0.01). Naloxone reversed the ethanol-induced depression of the hypercapnic hypoxic response in males, but had no effect on the female response. In males there was a direct correlation between the magnitude of the initial hypoxic response and the extent of depression by ethanol; the higher the response the greater the depression. Females showed a significant direct correlation between the blood alcohol and the increase in hypercapnic hypoxic slope, whereas males showed a weaker inverse correlation to blood alcohol level. These results demonstrate that ethanol depresses male but not female hypoxic ventilatory responsiveness and suggest that this is mediated by opioid-like mechanisms. Because the alcohol-induced depression was seen in subjects with a high control hypoxic response, the male-female difference might simply reflect initially lower control responses in females. This suggests a qualitative difference in hypoxic ventilatory control mechanisms between sexes.
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PMID:Ethanol-induced depression of hypoxic drive and reversal by naloxone--a sex difference. 320 79

Accidental rectal administration of 27 mg/kg of the narcotic analgesic Tramadol to a five-week-old infant resulted in severe cerebral depression, which had to be treated with Naloxone during 48 hours. The severity and the duration of this intoxication are not explained solely by the high dosage of Tramadol. A decreased elimination kinetics and an increased permeability of the blood-cerebrospinal fluid barrier probably also account for the pattern of the present intoxication.
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PMID:[Acute poisoning with a narcotic (Tramadol) in an infant of five weeks]. 322 Jul 91

Subcutaneous administration of the enkephalin analogue FK33-824 (FK) elicited a dose-related decrease in rectal temperature and respiratory rate in male ddY strain mice. Naloxone and 3 days' implantation of morphine pellet decreased the effects of FK, suggesting the involvement of opioid receptors and cross-tolerance with morphine to both effects of FK. A positive correlation was found between the FK-induced decrease in rectal temperature and that in respiratory rate among the 6 strains of inbred mice including BALB/c, C3H, A/J, CBA, C57BL/6 and DBA/2. The degree of hypothermia elicited by FK was different among strains, whereas marginal strain difference was seen in the respiratory depression induced by FK. The strain difference in the FK responses may be due to the difference in the opioid receptor subtypes in the brain.
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PMID:Effects of the enkephalin analogue FK33-824 on rectal temperature and respiratory rate in male mice. 322 53

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae. 329 87

This study assessed the effects of i.m. naloxone (10 mg) 6 hr after acute i.m. injections of morphine (0, 1, 3, 5.6, 10 and 17 mg). Naloxone reversed residual morphine-produced respiratory depression, miosis and subjective reports of drug "high." In addition, naloxone precipitated signs and symptoms characteristic of opioid withdrawal. Subjective report measures of "bad" drug effects and specific opioid withdrawal symptoms increased as a function of morphine pretreatment dose, as did observer-rated signs of withdrawal. Yawning was the most prominent observed sign, whereas yawning and irritability were the most consistently reported subjective symptoms. Peak withdrawal effects were seen within 15 min post-naloxone. The results of this study confirm previous reports of acute physical dependence in man and extend those findings by demonstrating a morphine dose-response function.
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PMID:Acute physical dependence in man: effects of naloxone after brief morphine exposure. 333 95


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