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 vast majority of morphine-sensitive single units in the area examined were localized to the locus coeruleus. This corresponds well with the known distribution of the highest densities of opiate receptor sites in this region of the midbrain. The effect of iontophoretically applied morphine was a marked and prolonged depression of spontaneous activity. Levorphanol, an opiate agonist, produced an effect similar to that of morphine while comparable doses of dextrorphan, it's clinically inactive stereoisomer, did not. Naloxone and levallorphan prevented as well as reversed the depression due to application of agonists. While the units were depressed following the application of opiate agonists, the cells were still excited by the neurotransmitter acetylcholine. We conclude that (1) neuronal sensitivity to opiates has a high positive correlation with autoradiographically determined opiate receptor sites, and (2) this sensitivity to opiates is blocked by opiate antagonists and is stereospecific in nature.
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PMID:Iontophoretic application of opiates to the locus coeruleus. 19 Nov 43

Morphine, levorphanol, dextrorphan and naloxone were applied microelectrophoretically to cells identified as either having nociceptive inputs or non-nociceptive inputs in the dorsal horn of the cat. Morphine excited non-nociceptive cells and depressed nociceptive cells. Naloxone reversed morphine excitations on non-nociceptive cells, but only reversed about one-third of morphine depressions on nociceptive cells. Levorphanol depressed nociceptive cells, whilst dextrophan ejected with similar currents caused less depression or had no effect. It is concluded that excitation of non-nociceptive cells may constitute a spinal action relevant to the analgesic action of opiates, acting synergistically with a depressant effect on nociceptive neurones.
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PMID:Differential excitatory and inhibitory effects of opiates on non-nociceptive and nociceptive neurones in the spinal cord of the cat. 63 89

The effect of microelectrophoretically and systemically applied opiates on neuronal discharge activity in the sensorimotor cortex of naive and morphine tolerant/dependent rats has been studied. In naive rats depression of spontaneous discharge activity was the predominant effect of low doses of phoretically applied morphine. Higher doses and repeated application frequently converted this effect into excitation. Only the depressant effect was antagonised by naloxone. Naloxone itself had no effect on spontaneous discharge activity when applied at dose-levels sufficient to antagonise the depressant effect of morphine. Levorphanol mimicked the action of morphine whereas dextrorphan was inactive. Morphine depressed the excitatory action of L-glutamate and of acetylcholine by a naloxone-antagonisable mechanism. Systemic application of Fentanyl mimicked the inhibitory effect of phoretically applied morphine upon transcallosally evoked discharge activity. The late response was markedly depressed whereas the primary response was little affected. Phoretically applied naloxone antagonised the effects of systemically applied Fentanyl. In chronically morphinised rats the depressant effect of microelectrophoretically administered morphine was almost lacking and a naloxone-resistant excitation became the predominant effect. In these animals the excitant effect of naloxone was also increased and the anti-glutamate effect and the anti-acetylcholine effect of morphine was abolished. The present data speak in favour of a postsynaptically located stereospecific receptor which mediates the inhibitory effects of opiates and which may be involved in the development of acute and chronic tolerance to these drugs.
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PMID:Actions of opiates upon single unit activity in the cortex of naive and tolerant rats. 98 31

In urethane-anesthetized rats, the effects of intravenous injections of morphine, levorphanol, dextrorphan, pentazocine and naloxone were studied studied on the activity in nerve fibres of the cervical sympathetic trunk, and on mean arterial blood pressure and heart rate. Impulse frequency in sympathetic nerve fibres was recorded with tungsten microelectrodes and proved to be more sensitive to drug action than blood pressure or heart rate. Morphine 1 and 2 mg/kg dose dependently reduced sympathetic impulse frequency, blood pressure and heart rate; morphine 0.5 mg/kg was ineffective. Levorphanol 1 and 2 mg/kg dose dependently reduced sympathetic impulse frequency and blood pressure but did not affect heart rate. Dextrorphan (the dextro-isomer of levorphanol) 2 and 4 mg/kg had no effect on the parameters tested. Pentazocine 3 and 6 mg/kg did not cause a consistent change in sympathetic impulse frequency, blood pressure and heart rate. Naloxone 0.2 mg/kg abolished the depressant effects of morphine and levorphanol and, when given alone, increased sympathetic impulse frequency. Naloxone 1 mg/kg increased blood pressure but did not affect heart rate. It is concluded that morphine can reduce blood pressure and heart rate by causing opiate-specific central sympathetic depression.
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PMID:Depression by morphine and levorphanol of activity in sympathetic nerve fibres in anaesthetized rats. 674 20

The mu-opioid receptor antagonist effects of naloxonazine on levorphanol-induced thermal antinociception and respiratory depression were examined in rhesus monkeys. Levorphanol (0.032-3.2 mg/kg) produced dose-dependent increases in tail-withdrawal latencies from 50 degrees C water in a warm-water tail-withdrawal assay and dose-dependent decreases in ventilation in both air and 5% CO2 mixed in air. Naloxonazine (0.1-3.0 mg/kg) antagonized both the antinociceptive and ventilatory effects of levorphanol to a similar degree, and the antagonist effects of naloxonazine were greater after 1 h than after 24 h. Under all conditions, the antagonist effects of naloxonazine were fully surmountable. Schild analysis of the antagonist effects of naloxonazine after 1 h pretreatment in the antinociception assay yielded a pA2 value of 7.6 and a slope of -0.50; by comparison, quadazocine yielded a pA2 value of 7.5 and a slope of -1.05. These results suggest that naloxonazine acts as a potent and fully reversible mu-opioid receptor antagonist with a moderately long duration of action in rhesus monkeys. In addition, these results suggest that the antinociceptive and ventilatory effects of mu-opioid receptor agonists in rhesus monkeys are mediated by pharmacologically similar populations of mu opioid receptors.
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PMID:Naloxonazine antagonism of levorphanol-induced antinociception and respiratory depression in rhesus monkeys. 886 16

Affective states are regulated mainly by serotonin and noradrenaline. However the opioid system has been also related to antidepressant-induced mood improvement, and the mu-opioid receptor has been involved in affective responses to a sustained painful stimulus. Similarly, antidepressant drugs induce an antinociceptive effect via both the monoaminergic and opioid systems, probably involving sensorial and affective dimensions of pain. The aim of this study was to test three opiate analgesics, which also inhibit monoamine reuptake, in the learned helplessness model of depression in rats. Helpless rats receiving (+/-)tramadol (10, 20 mg/Kg) or (-)methadone (2, 4 mg/Kg) showed a decreased number of failures to avoid or escape aversive stimulus (shock) in both the second and the third daily sessions, compared with controls. Rats receiving levorphanol (0.5, 1 mg/Kg) showed a decreased number of such failures in the third session. The number of crossings in the intertrial interval (ITI) was not significantly modified by (+/-)tramadol or (-)methadone. Levorphanol enhanced ITI crosses at 1 mg/Kg. These results, together with other clinical and experimental data, suggest that analgesics with monoaminergic properties improve mood and that this effect may account for their analgesic effect in regulating the affective dimension of pain. From this, it seems probable that the analgesic effect of opiates could be induced by adding together the attenuation produced of both the sensorial and the affective dimensions of pain.
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PMID:Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. 1241 48