β-Blockade of morphine-induced hyperlactacidemia in rabbits

Summary In morphinized rabbits blood lactate levels are elevated. Hyperlactacidemia perists after cessation of morphine injections. This morphine-induced lactate accumulation is completely abolished by simultaneous propranolol treatment. Phentolamine does not modify the action of morphine.ERA CNRS No. 412.Acknowledgement. The authors express their appreciation to MissD. Abadie for her help with the lactate determinations.     

Facilitation or inhibition of memory by morphine: a question of experimental parameters

The effects of morphine on memory are highly controversial. According to some investigators post-trial injections of morphine facilitate memory. Others, however, have reported impairment of memory after morphine injections. To investigate the extent to which this may be due to different experimental parameters, foot-shock intensity and dosage of morphine were systematically varied in a passive-avoidance task. It was found that post-trial administration of medium and relatively high doses of morphine facilitate retention performance following moderate levels of foot-shock. Under other conditions of dose and shock intensity, the drug was not effective or even impaired retention.     

Role of the Raphe Magnus nucleus in morphine analgesia : studies with intracerebral microinjections in the rat]

Microinjections of low concentration of morphine (5 micrograms) into the nucleus Raphé Magnus of the Rat produce a strong analgesia that can be reversed by systemic naloxone, an opiate antagonist. The administration of naloxone (5 micrograms) into the Raphé Magnus considerably reduces the effects of intravenous morphine. The effects of microinjections of morphine are strongly reduced by Cinanserin, suggesting a role for serotoninergic mechanisms in morphine analgesia.     

Facilitation or inhibition of memory by morphine: a question of experimental parameters

Summary The effects of morphine on memory are highly controversial. According to some investigators post-trial injections of morphine facilitate memory. Others, however, have reported impairment of memory after morphine injections. To investigate the extent to which this may be due to different experimental parameters, foot-shock intensity and dosage of morphine were systematically varied in a passive-avoidance task. It was found that post-trial administration of medium and relatively high doses of morphine facilitate retention performance following moderate levels of foot-shock. Under other conditions of dose and shock intensity, the drug was not effective or even impaired retention.Results presented in part at the EBBS Meeting in Louvain-la-Neuve (Belgium), November 1980.     

Effect of chronic administration of morphine on primary immune response in mice

Summary The effect of 3 different doses of chronically-administered morphine on the primary immune response was studied in mice by estimating spleen/body weight ratio and serum hemolysin production against sheep red blood cells (SRBC). It was observed that morphine exerted a dose-dependent inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. The findings suggest that the inhibitory effect of morphine is specific.     

Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype

We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [³H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present. Received 1 November 2001; received after revision 1 February 2002; accepted 1 February 2002     

The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

Morphine eye-drops reduce homatropine induced mydriasis in man

Summary In 7 healthy volunteers 4% morphine eye-drops, when administered to one eye, caused a miosis limited to that eye. In 7 other healthy volunteers morphine was administered into one eye after bilateral instillation of 0.5% homatropine opthalmic drops; the eye treated with morphine and homatropine showed a mydriasis less intense than the other eye treated only with homatropine. It is suggested that topical morphine locally affects sympathetic function by inhibiting noradrenaline release into the iris neuromuscular junction.This work was partly supported by the CNR study group Pain Control. The authors wish to thank Dr Tendi of the Pharmacy of St. Maria Nuova Hospital, Florence, for the preparation of the eye-drops.     

Morphine suppression of ethanol withdrawal in mice

Summary The acute administration of morphine, alcohol or dopamine results in a pronounced suppression of the convulsions produced by alcohol in mice. The suppressive action of morphine on alcohol withdrawal in the mouse apparently is not a product of morphine intoxication, but rather to some other specific interaction between alcohol and morphine in the central nervous system. The conclusion suggest that dopamine may play a significant role as a modulator in convulsions produced during alcohol withdrawal.Dr.Kenneth Blum is Associate Professor in Pharmacology at The University of Texas Health Science Center at San Antonio and a Career Teacher in Drug Abuse and Alcoholism under a grant number 1-TO1-DA00290-01 from the National Institute on Drug Abuse.Acknowledgments. Our thanks are due toB. Wiggins, R. Marin andS. Elston for their excellent technical assistance. Research funded in part by Air Force Grant No. AFOSR-71-2075.     

Hemmung von Morphin-Effekten durch synthetische Substanz P

Summary Synthetic Substance P and naloxone abolish the proconvulsive action of morphine on pentetrasol-induced seizures. It is suggested that Substance P could be a natural antagonist of morphine in the central nervous system.

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Am 20. März 1976 gestorben.     

Comparative activity of endorphins on the opiate receptors]

Displacement of naloxone from membranes of Rat brain by alpha, beta and gamma-endorphins with and without Na+ in the incubating medium has been studied. beta-endorphin shows a higher affinity for the opiate receptors and a stronger agonist property than morphine. alpha and gamma-endorphins have a much lower affinity than morphine and a marked antagonist characteristic. This study suggests the possibility of naturally occurring antagonists of the opiate receptors.     

Lipid accumulation in mouse hepatocytes after morphine exposure

Summary After morphine injection lipid accumulation in mouse hepatocytes begins within 2 h and continues for 24 h when most hepatocytes are filled with lipid droplets. In spite of morphine maintenance the liver recovers as the accumulated lipids are coupled with protein and subsequently transported and released into the perisinusoidal space of Disse.Supported by USPHS Grants GM 15490, 5 SO7 RR05386-16 and DA-01310.     

Effects of d1-methadone and morphine on developing chick embryo

Summary Injections of methadone into the air space of fertile chicken eggs affected development of the embryo. Both methadone and morphine caused decreases in liver weight and brain protein, and morphine increased liver protein levels.Acknowledgment. We thank E. Sutherland for technical assistance. Supported by a grant from the Department of Health and Welfare, Canada, and the British Columbia Ministry of Health, Alcohol and Drug Commission.     

Improving the thermal stability of lactate oxidase by directed evolution

Lactate oxidase is used in biosensors to measure the concentration of lactate in the blood and other body fluids. Increasing the thermostability of lactate oxidase can significantly prolong the lifetime of these biosensors. We have previously obtained a variant of lactate oxidase from Aerococcus viridans with two mutations (E160G/V198I) that is significantly more thermostable than the wild-type enzyme. Here we have attempted to further improve the thermostability of E160G/V198I lactate oxidase using directed evolution. We made a mutant lactate oxidase gene library by applying error-prone PCR and DNA shuffling, and screened for thermostable mutant lactate oxidase using a plate-based assay. After three rounds of screening we obtained a thermostable mutant lactate oxidase, which has six mutations (E160G/V198I/G36S/T103S/A232S/F277Y). The half-life of this lactate oxidase at 70 °C was about 2 times that of E160G/V198I and about 36 times that of the wild-type enzyme. The amino acid mutation process suggests that the combined neutral mutations are important in protein evolution. Received 15 September 2006; received after revision 21 October 2006; accepted 2 November 2006     

Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells

We have observed that treatment of human glioma cells with morphine in the nanomolar range of concentration affects the mitochondrial membrane potential. The effect is specific to morphine and is mediated by naloxone-sensitive receptors, and is thus better observed on glioma cells treated with desipramine; moreover, the mitochondrial impairment is not inducible by fentanyl or methadone treatment and is prevented by the nitric oxide (NO) synthase inhibitor L-NAME. We conclude that in cultured glioma cells, the morphine-induced NO release decreases the mitochondrial membrane potential, as one might expect based on the rapid inhibition of the respiratory chain by NO. The identification of new intra-cellular pathways involved in the mechanism of action of morphine opens additional hypotheses, providing a novel rationale relevant to the therapy and toxicology of opioids.Received 19 August 2004; received after revision 16 September 2004; accepted 7 October 2004     

The effects of acute and chronic morphine on regional distribution of cardiac output in brain

Summary Both acute and chronic administration of morphine resulted in an increase in the percent cardiac output received by brain. However, various brain regions were affected differently by the drug treatments. The greatest increases in percent cardiac output received after chronic administration of morphine occurred in pons and cerebellum, while the greatest increases after acute administration occurred in cortex and midbrain. The changes found are in contrast with earlier studies which suggest that morphine has no effect on cerebral blood flow.     

Prolactin and growth hormone releasing activity of [D-Met2, Pro5]-enkephalinamide in the rat after systemic administration

Summary The growth hormone (GH) and prolactin releasing (PRL) activity of [D-Met², Pro⁵]-enkephalinamide (EKNH₂), an opioid peptide analog with higher opiate agonist activity that morphine, was compared in the unanesthetized male rat to those of equimolar doses of morphine upon systemic injection. EKNH₂ proved to be a higher PRL, but not GH, releaser than the opiate alkaloid.     

Morphine selectively facilitates the inspiratory-inhibitory vagal reflex in adult rabbits

In rabbits naive to opiates or pretreated with morphine a selective morphine-induced facilitation of the Breuer-Hering inflation reflex is described.     

Influence of hydrochlorothiazide on the pain threshold and on the antinociceptive activity of morphine, in rats

Hydrochlorothiazide, acutely injected in rats, has a weak analgesic activity per se and potentiates and prolongs the antinociceptive effect of morphine.