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)

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.
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PMID:Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide. 131 Feb 49

Intracellular recordings were made from neurons in a rat locus coeruleus slice preparation in vitro. A postsynaptic potential was evoked by electrical stimulation of afferents to the neurons. CI-977 ([5R-(5a,7a,8b)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec -8-yl[-4-benzofuranacetamide monohydrochloride) caused a depression of the evoked postsynaptic potential on locus coeruleus neurons. This action was reversed on washout. Bremazocine had a similar action on less than 50% of locus coeruleus neurons. Concentrations of CI-977 which depressed the postsynaptic potential did not affect either passive membrane conductance or a voltage-sensitive potassium current resembling IA. The depression of the excitatory postsynaptic potential caused by CI-977 remained in the presence of either 30 microM bicuculline and picrotoxin or when potassium acetate-filled recording electrodes were used. Using potassium chloride-filled recording electrodes and in the presence of 30 microM 6-cyano-2,3-dihydro-7-nitroquinoxaline-2,3-dione and either 30 microM DL-2-amino-5-phosphonovaleric acid or 500 microM kynurenic acid, CI-977 had no effect on the postsynaptic potential. The effects of CI-977 were reversed by 30-100 nM naloxone and 1-10 nM norbinaltorphimine but not by 1-10 nM naloxone. The hyperpolarizing response to the mu-opioid receptor-selective agonist D-Ala2,Nme Phe4,Gly-ol5 (DAGOL) was blocked by 1-10 nM naloxone but not by 1-100 nM norbinaltorphimine. The hyperpolarizing response to DAGOL was not affected by high doses of CI-977.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A highly selective kappa-opioid receptor agonist, CI-977, reduces excitatory synaptic potentials in the rat locus coeruleus in vitro. 131 40

We evaluated in human monocytes the effect of high doses of alfentanyl on the expression of vimentin filaments, the phagocytic activity and the membrane display of HLA-DR molecules in the subjects undergoing surgery. The study was performed on 30 patients, ASAI-II. The patients received 100 mcg/kg i.v. of Alfentanil and the maintenance of anaesthesia was made with Alfentanil (2-3 mcg/kg/min.). The patients were randomized in two groups. The patients were ventilated with N2O:O2 (1:1) (Group I) or air: O2 (1:1) (Group II). After surgery, all patients of the Group II received Naloxone (0.2-0.4 mg). Central venous blood samples were obtained before induction, one and two hours after induction of anaesthesia and at the end of surgery. Separation of monocytes was performed according to Boyum technique. CD35 and HLA-DR molecules and vimentin filaments were studied by indirect immunofluorescence method using monoclonal antibodies. Percentage of positive cells were read with a cytofluorometer. The phagocytic function of monocytes was determined by ingestion of latex particles. Cortisol and ACTH plasma levels were determined by RIA. High doses of Alfentanyl depress phagocytic function and membrane display of CD35 and HLA-DR molecules in monocyte and induce marked changes in the organization of vimentin filaments in these cells in patients undergoing surgery. This monocytic depression was more marked in the patients ventilated with N2O. In our results there was uninhibition of ACTH and cortisol plasma levels responses to surgical stress by Alfentanil administration. Since the effects of Alfentanil were reversed by Naloxone, an opioid receptor mechanism seems to mediate these events.
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PMID:[Depression of the mononuclear phagocyte system caused by high doses of narcotics]. 133 12

1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of beta-endorphin (0.01, 0.1 and 1.0 nmol kg-1) were examined in conscious rabbits. 2. After i.c.v. beta-endorphin, mean arterial pressure (MAP) increased, heart rate (HR) fell, plasma noradrenaline, adrenaline and glucose increased and there was a rise in PaCO2 and fall in PaO2; these effects were reversed by intravenous (i.v.) naloxone (300 nmol kg-1). 3. A combination of prazosin (2 mg kg-1) and yohimbine (1 mg kg-1), given i.v., prevented the rise in MAP induced by i.c.v. beta-endorphin. 4. After i.c. beta-endorphin, MAP, HR and plasma catecholamines were not significantly altered but there was a similar degree of respiratory depression. 5. Clonidine (1.0 micrograms kg-1, i.c.) reduced MAP and HR; these effects were not blocked by i.v. naloxone (6 mumol kg-1). 6. These results demonstrate that beta-endorphin acts centrally, probably mainly on periventricular mu-opioid receptors, to increase adrenaline secretion and sympathetic nerve activity leading to alpha-adrenoceptor-mediated vasoconstriction. The respiratory depression is probably mediated by brainstem mu-receptors. 7. A role for beta-endorphin in the central hypotensive action of alpha 2-adrenoceptor agonists was opposed by finding that opioid receptor antagonism with naloxone did not block the effects of clonidine.
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PMID:The pressor response to central administration of beta-endorphin results from a centrally mediated increase in noradrenaline release and adrenaline secretion. 136 32

Until recently, only the racemic mixture of ketamine has been used in anaesthesia. Little is known of the central nervous effects of the pharmacologically more potent S(+)-isomer. Information in regard to the putative receptor site involved in the mediation of its anaesthetic/analgesic effect is particularly sparse. METHODS. In order to evaluate the anaesthetic and antinociceptive properties of S(+)-ketamine, a dose-response relationship of the compound on the EEG, somatosensory-evoked potentials (SEP), and respiration was established. Increasing doses (2, 5, 10, 20 mg/kg) were given to trained and awake dogs (n = 10) at 10-min intervals. In order to detect a possible opioid receptor-related interaction, an antagonist of the methoxymorphinane series (cyprodime 80 g/kg i.v.) with higher selectivity than naloxone for the mu-receptor was given at the end. RESULTS. Compared to controls, S(+)-ketamine induced a dose-related increase in output in the theta-(3-8 Hz) band and an increase in output in the alpha-domain (8-13 Hz) following 20 mg/kg. Both effects were reversed completely by the opioid antagonist. At low doses (2-5 mg/kg) there was an increase in output (P less than 0.05) in the beta-(13-30 Hz) and a concomitant decrease in output (P less than 0.05) in the delta-(0.5-3 Hz) band. These effects were reversed with increasing doses (5-10 mg/kg). After 20 mg/kg, however, output in the delta-domain increased while power in the beta band decreased significantly (P less than 0.005) when compared to controls. Both effects were reversed by the opioid antagonist. Compared to controls, the reversal resulted in a 12% increase in output in the beta- and a 49% decrease in output in the delta-domain. In SEP, S(+)-ketamine induced a dose-related increase in peak latency and depression of amplitude of more than 50% when compared to controls. While latency changes were completely reversed, amplitude height was only partly restored by the antagonist. Respiration was depressed in a dose-related fashion (PaO2 decreased, PaCO2 increased). Hypoxaemia was fully reversed by the antagonist; hypercapnia was only partly reversed. CONCLUSION. The results support the presumption that the S(+)-isomer of ketamine induces opioid mu-receptor-mediated central effects. Hypersynchronisation of the EEG suggests a deep plane of anaesthesia after S(+)-ketamine. The pronounced blockade of impulses in the sensory nervous pathways suggests an efficient analgesic effect that is partly mediated by the opioid-receptor. The respiratory depression may be of importance when S(+)-ketamine is used in high dosages in man.
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PMID:[Pharmacodynamic effects of S-(+)-ketamine on EEG, evoked potentials and respiration. A study in the awake dog]. 141 7

Antinociception and central nervous system depression (CNSD) caused by intraperitoneal, intrathecal and subcutaneous administration of oxycodone or morphine were studied in a randomized and blind, saline controlled study in rats. Antinociception was assessed with the tail-flick and hot plate tests. CNSD was assessed by testing the corneal, placing and righting reflexes and with a 4-point catalepsy score. Intraperitoneally and subcutaneously administered oxycodone and morphine were given in doses of 2.5-10 and 5-20 mg kg-1 respectively. The intrathecal doses were 12.5 micrograms and 100 micrograms of oxycodone and 6.25 micrograms and 50 micrograms of morphine. In both nociceptive tests subcutaneously and intraperitoneally administered oxycodone was 2-4 times more potent than morphine, while intrathecal morphine was over 14 times more potent. CNSD was more profound with oxycodone than with morphine after intraperitoneal and subcutaneous administration, but was not observed after intratechal administration of either drug. Differences in opioid receptor affinities, liposolubilities and metabolism are discussed as possible explanations.
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PMID:Antinociceptive effects and central nervous system depression caused by oxycodone and morphine in rats. 150 38

Two independent clinical trials were conducted simultaneously. In one, tramadol and pethidine were compared in 30 patients by patient-controlled analgesia during the first 24 h following abdominal surgery. The mean 24 h consumption of tramadol and pethidine was 642 mg and 606 mg respectively, giving a potency estimate of tramadol relative to pethidine of 0.94 (95% confidence interval 0.72-1.17). In the second trial, the effect on respiration of three doses of tramadol (0.5, 1.0, and 2.0 mg.kg-1) was compared with that of morphine sulphate (0.143 mg.kg-1) by intravenous injection during stable halothane anaesthesia. At approximately 1.5 times the equipotent dose, as estimated from the first trial, tramadol transiently depressed the rate of respiration but had no effect on end-tidal carbon dioxide tension. Morphine caused apnoea or considerable depression of ventilation. The results suggest that mechanisms other than opioid receptor activity play a significant role in the analgesia produced by tramadol.
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PMID:Tramadol: pain relief by an opioid without depression of respiration. 151 77

The effect of tramadol on laryngeal reflex activity was assessed in a double-blind cross-over study in six volunteers receiving single oral doses of either codeine 50 mg, tramadol 50 mg or tramadol 100 mg. Laryngeal reactivity was measured by the response to the inhalation of dilute ammonia vapour. The minimum ammonia concentration required to induce a glottic stop was recorded prior to drug administration, and at 15, 30, 45, 60, 90, 120, 150 and 180 min thereafter. Psychometric tests were performed at 0, 45 and 105 min to detect any relationship between central sedation and changes in laryngeal reflex activity. The concentration of ammonia required to induce a glottic stop increased in all treatment groups, but more so in the tramadol groups. The time course suggested that the codeine effect peaked early, and had returned to normal within 2 h. For tramadol 100 mg, laryngeal depression appeared to be still increasing at the end of the 3-h study period. No correlation was found between laryngeal and sedative effects. Tramadol is produced as a racemic mixture, in which one isomer acts through an opioid receptor pathway whilst the other affects noradrenergic and serotonergic mechanisms. Both of these routes of action may be involved in the suppression of the response to experimentally induced cough.
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PMID:A comparison of the effects of codeine and tramadol on laryngeal reactivity. 155 50

The principles of positron emission tomography (PET) are described, and illustrations of how these can be applied to clinical psychiatric questions relating to schizophrenia and depression are delineated. The metabolic changes in the frontal lobes which have been described in both depression and schizophrenia and depression are reviewed and discussed. More recent PET techniques allow several serial measurements of changes in regional blood flow in response to either a pharmacological challenge or a specific psychological task. This method provides a promising new approach to the study of the dopaminergic system in schizophrenia. New tracer methods of quantitating changes in in vivo concentrations of opioid receptors allow direct pharmacological access to the endogenous opioid system in the brain. Observations of regional cortical differences in opioid receptor concentration in relation to the medial and lateral pain systems are described. In addition, changes in receptor occupancy during sleep using [11C]diprenorphine and changes in the mu-specific tracer [11C]carfentanil in temporal lobe epilepsy are discussed.
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PMID:Positron emission tomography as a research tool in the investigation of psychiatric and psychological disorders. 164 17

1. The influence of the delta-opioid receptor agonist (D-Ser2)-leu-enkephalin (Thr6) (DSLET) on different spinal reflex pathways was investigated in anaemically decapitated, high spinal cats. Monosynaptic reflexes were tested to analyse excitatory and inhibitory flexor reflex afferent (FRA) pathways from nociceptive (from the skin of the central pad) and non-nociceptive (from skin, joint or group II muscle) afferents, as well as an excitatory nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors and the inhibitory pathway from Ib muscle afferents. 2. DSLET suffused over the spinal cord (concentration 10(-3)-10(-6) M) caused a concentration-dependent depression of transmission in nociceptive and non-nociceptive FRA pathways. The excitatory FRA pathways including those from group II muscle afferents were more sensitive than the inhibitory ones. The nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors was less affected than the FRA pathways. The inhibitory pathway from Ib muscle afferents remained almost unaffected. 3. Intravenous injection of DSLET (0.5-3.6 mg/kg) induced dose-dependent effects similar to those from local spinal application. The main difference was that I.V. injection more readily caused depression of the inhibitory FRA pathways to extensors. 4. The effects of local spinal application and of I.V. injection of DSLET were antagonized by I.V. injection of naloxone (0.1-1 mg/kg). 5. The effects of DSLET on spinal reflex pathways in many respects resemble that of monoamines. Possibly there is an interaction and a co-operation of enkephalins and monoamines in motor control.
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PMID:Limitedly selective action of a delta-agonistic leu-enkephalin on the transmission in spinal motor reflex pathways in cats. 166 54


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