Depressant Action Of Morphine Research Articles

The depressant action of morphine on transmission at a skeletal neuromuscular junction is non-specific.

Abstract The depressant actions of apomorphine, etorphine, dextromoramide, laevomoramide, naloxone, codeine, morphine and nalorphine have been examined on the rat diaphragm preparation. Their descending order of potency (in the order given above) differed greatly from that published for activity at specific opiate receptors. The depressant action of morphine was not antagonized by naloxone. The stereoisomers dextro- and laevomoramide were equipotent in depressing the preparation. On the transmurally stimulated guinea-pig ileum preparation the depressant action of dextromoramide was antagonized by naloxone. Laevomoramide was 10 000 times less potent than its (+)-isomer, and was not antagonized by naloxone. It is concluded that the effects of narcotic analgesics on transmission at a skeletal neuromuscular junction are not mediated via opiate receptors.

Chronic treatment with naltrexone enhances morphine-stimulated dopamine neurotransmission: Neurochemical and behavioral evidence

Rats were implanted for 10 days with a slow-release pellet of naltrexone or were given sham surgery. At one of various different intervals during or after implantation of the pellet, the synthesis of dopamine (DA) was assessed in the nigrostriatal and mesolimbic systems. The results indicated that naltrexone alone was without effect on the synthesis of DA. However, one day after removal of the pellet, naltrexone-treated animals displayed an enhanced response to the DA-stimulatory action of morphine (15 mg/kg) in both the nigrostriatal and mesolimbic systems. This change was accompanied by an increase in specific binding of the μ-specific radioligand [ 3H]DAGO in whole brain and by an increase in the depressant action of morphine on locomotor activity. In contrast, at 10 days after removal of the pellet, naltrexone was without effect on morphine-induced changes in the synthesis of DA and locomotor activity, thus indicating that the supersensitivity to morphine was transient. These results support the idea that opioids modulate DAergic neurotransmission in the nigrostriatal and mesolimbic pathways and that this modulatory role may underlie opiate-induced changes in locomotor behavior.

Separation of Opioid Analgesia from Respiratory Depression

Pretreating rats 24 hr earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P less than .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.

Morphine enhances adenosine release from the in vivo rat chemical cortex

Morphine (1 and 5 mg/kg), administered intravenously, increased the rate of efflux of purines from intact rat cerebral cortises prelabelled with 3H-adenosine. Naloxone antagonized morphine's action. It is suggested that the depressant actions of morphine on transmission in the central nervous system may be related to this enhancement of extracellular levels of adenosine and the adenine nucleotides.

PHARMACOLOGICAL AND ELECTROPHYSIOLOGICAL STUDIES OF MORPHINE AND ENKEPHALIN ON RAT SUPRASPINAL NEURONES AND CAT SPINAL NEURONES

1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.

The Increase of the Epinephrine Output under Morphine depends upon the Integrity of the Splanchnic Nerves

The suprarenal vein blood was collected from the dogs in the conditions as physiological as possible, and its epinephrine content was determined by means of the rabbit intestine segment. Morphine hydochloride was injected into a saphena vein in dose of 8mg per kg of body weight in 30 seconds. Interference with the splanchnic nerves totally abolishes the augment-ing action of morphine upon the epinephrine output rate from the gland on that side. Double splanchnicotomy nearly totally abolishes the appearance of hyperglycemia due to morphine, while the depressant action of morphine upon the arterial blood pressure does not suffer therefrom.