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)

Morphine caused in the anaesthetized rat reduction in brain noradrenaline (NA) turnover, hypotension and bradycardia, similarly to the antihypertensive, alpha-adrenergic agonist, clonidine. All effects of morphine were antagonized by naloxone, as well as the alpha-receptor antagonist, yohimbine. In contrast, naloxone did not affect the circulatory depression and reduction in brain NA utilization by clonidine which both previously have been found to be antagonized by yohimbine. In contrast to clonidine, morphine even in high doses did not facilitate the flexor reflex activity of acutely spinalized rats. Pretreatment with protriptylin largely attenuated the circulatory depressive effects of morphine, as it has previously been found to block the corresponding effects of clonidine. Thus, the morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors. However, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.
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PMID:Evidence for involvement of central noradrenergic neurons in the cardiovascular depression induced by morphine in the rat. 97 95

The effect of acute administration of morphine on cerebral excitability was investigated in rats with two convulsant drugs: flurothyl (hexafluorodiethyl ether) and pentylenetetrazol (PTZ). In the flurothyl study, adult male Sprague-Dawley (S-D) rats were injected subcutaneously with morphine sulfate in doses ranging from 0.5 to 256 mg/kg. At 15, 30, 60 and 120 minutes after morphine injection, flurothyl was administered by inhalation and the seizure thresholds were determined. In the PTZ study, 64 mg/kg of morphine sulfate were injected subcutaneously into both S-D and CFN (Wistar-derived) rats. Thresholds to PTZ seizures were measured after administering the convulsant either by the intraperitoneal or intravenous route. The data revealed an anticonvulsant action of morphine on both flurothyl and PTZ. Peak time for this effect on flurothyl seizures was 30 minutes after subcutaneous administration of the opiate, with the maximal anticonvulsant activity appearing at the 64-mg/kg dose. The increase in seizure threshold in S-D rats at this dose was 36% with flurothyl, 94% with intravenous PTZ and 352% with i.p. PTZ. Morphine had a less dramatic influence on raising the latter seizure threshold in the CFN than in the S-D strain. The graded dose-related anticonvulsant action is independent of the respiratory depression associated with morphine administration and appears to be a reflection of an altered central nervous system excitability produced by the narcotic in rats.
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PMID:Anticonvulsant action of acute morphine administration in rats. 97 66

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

By subcutaneous implantation of 2 or 13 morphine pellets (75 mg morphine/pellet), rats were made tolerant to, and dependent on narcotic analgesics. Occipital cortex slices from dependent animals and placebo-implanted controls were incubated with (-)-3H-noradrenaline and subsequently superfused with physiological salt solution. The accumulation of 3H-noradrenaline was not changed by pretreatment with 2, but was slightly decreased by pretreatment with 13 morphine pellets. The overflow of tritium evoked by electrical field stimulation was higher in slices from morphine-implanted rats than in those from placebo controls. Morphine and levorphanol, added in vitro, inhibited the stimulation-induced overflow of tritium at similar concentrations and to a similar degree in slices from morphineand placebo-pretreated animals.--It is concluded that, during chronic treatment with morphine, an adaptation takes place in the brain to compensate for the acute effect of narcotic analgesics, i.e. inhibition of the release of noradrenaline by nerve impulses. The chain of events from the drug-receptor interaction to the depression of the release process can be escluded as substrate of this adaptation. During withdrawal, the compensatory changes provoke an enhanced increase of extracellular noradrenaline during nerve impulses.
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PMID:Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex. 123 93

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

The effect of morphine on the ascending excitatory reflex of the circular muscle elicited by radial distension of the gut wall was studied in the isolated guinea-pig small intestine. A three compartment bath, in which an intermediate compartment divided the site of intraluminal stimulation (caudal compartment) from the site of reflex contraction recording (oral compartment), was used. Morphine (0.01-10 microM) applied independently to each compartment, caused a concentration-dependent depression (up to 90%) of the amplitude of distension-evoked reflex contractions. Concentration-response curves to morphine were shifted to the right by naloxone (30 nM) with an apparent pA2 value of about 8.5, which suggests an interaction with opioid mu-receptor subtypes. Our results indicate that morphine not only depressed transmission from excitatory motor neurons to the circular muscle but also neuro-neuronal transmission along the ascending excitatory reflex pathway.
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PMID:Sites of action of morphine on the ascending excitatory reflex in the guinea-pig small intestine. 133 12

Domestic fowl tested at 3, 5, and 7 days posthatch jumped from a heated grid more rapidly than animals tested at 14 days posthatch. Morphine (2.5 mg/kg) decreased jump latency in 14-day-old chicks but did not significantly affect jump latency in younger chicks. Respiration was lower in 3-day-old chicks than in the older groups but morphine depressed respiration at each age. In a second experiment morphine significantly decreased jump response latency in 5-day-old chicks when thermal stimulus intensity was lowered and morphine dose increased (5 mg/kg). Posttest respiration rate was depressed by morphine. Morphine hyperalgesia and respiratory depression were reversed by naloxone (5 mg/kg). However, naloxone alone increased jump response latency. Young domestic fowl are more sensitive and/or reactive to a noxious thermal stimulus and are less sensitive to morphine than 14-day-old chicks but morphine hyperalgesia was evident in both 5- and 14-day-old chicks. These hyperalgesic chicks may be tolerant at birth to morphine hypoalgesic effects on nociception.
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PMID:Morphine hyperalgesic effects on developmental changes in thermal nociception and respiration in domestic fowl (Gallus gallus). 140 87

The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6-glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion.
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PMID:Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. 141 Jan 47

The effect on in vitro migration of leucocytes and lymphocytes of various drugs used in anaesthesia have been determined in the concentration range 10(-2) to 10(-6) M. The drugs included, thiopentone, bupivacaine, lignocaine, adrenaline, noradrenaline, hydrocortisone, morphine (with and without preservative), lorazepam, suxamethonium, pancuronium and atropine. Toxicity and effect on random mobility after incubation for 1 and 18 h were also determined. Thiopentone depressed leucocyte function at a concentration of 10(-5) M which is comparable to clinical plasma concentrations. Increasing the duration of exposure of the cells to the drugs significantly lowered the concentrations at which depression of function was observed. At concentrations used during local infiltration in clinical practice, bupivacaine and lignocaine were toxic to both leucocytes and lymphocytes. Adrenaline, whilst having no direct effect on cell function, potentiated the effect of lignocaine. Morphine showed no effect at 10(-4) M, a level 1,000 times greater than the reported toxic plasma levels. However, this level falls within the range reported for drug addicts. No effects were found for the other drugs.
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PMID:Leucocyte migration: effects of in vitro exposure to anaesthetic agents: possible potentiation of effects by adrenaline. 142 14

Effect of cocaine on morphine-induced analgesia and the accompanying respiratory depression, bradycardia and hypolocomotion/sedation was studied in rats. Cardiovascular and respiratory effects were studied under pentobarbitone-induced anaesthesia. Cocaine enhanced morphine-induced analgesia in the formalin test, hot plate test and heat-induced tail withdrawal test in intact rats. However, in spinal rats a similar combination of cocaine with morphine did not produce increased latencies in the tail withdrawal test. Of the three analgesic tests used, the formalin test was the most sensitive to the enhancement, as well as to the effects of morphine or cocaine alone. Morphine at the dose of 6 mg/kg produced complete analgesia in the formalin test, significant hypolocomotion/sedation, significant bradycardia and significant decrease in the respiratory rate. At an equianalgesic dose (complete analgesia in the formalin test) of morphine (3 mg/kg)-cocaine (5 mg/kg)-combination no significant changes in heart rate, respiratory rate or locomotion(/alertness) were observed. Changes in skin blood flow determined by the laser Doppler flow method were not significant in any of the experimental conditions. The results indicate that cocaine enhances morphine-induced analgesia, mainly due to supraspinal mechanisms. In contrast, the morphine-induced bradypnoea, bradycardia and hypolocomotion/sedation are attenuated by cocaine.
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PMID:Enhancement of morphine-induced analgesia and attenuation of morphine-induced side-effects by cocaine in rats. 143 38


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