Naloxone prevents the analgesic action of alpha-MSH in mice

alpha-MSH (0.1, 1, 10 micrograms) was administered intracerebroventricularly and its action on pain sensitivity was investigated by the hot-plate method in mice. alpha-MSH produced dose-dependent analgesia and this analgesic effect was prevented by naloxone (1 mg/kg, s.c.). It is possible that alpha-MSH may play a role in the mechanism of pain through endogeneous opioid systems.     

Circling behavior induced by phencyclidine in mice and its inhibition by naloxone

Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.     

Differential effects of opiates on the incorporation of [14C] thiamine in the central nervous system of the rat

Summary Opiate agonist (morphine), pure antagonist (naloxone), mixed agonist-antagonist (nalorphine) and analgesically inactive enantiomorph (dextrorphan) produced differential stereoselective effects on the incorporation of [¹⁴C] thiamine in the central nervous system of the rats. The possible role of thiamine in opiate effects and its implications are discussed.To whom reprint requests should be addressed. The authors thank Dr. S. J. Mulé, Assistant Commissioner and Director, ODAS Testing and Research Laboratory, for his kind interest and support and Mrs J. Vardy, Mr A. Kramer and Mr V. Aschettino for assistance.     

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.     

Circling behavior induced by phencyclidine in mice and its inhibition by naloxone

Summary Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.Acknowledgment. We are grateful to Professor A. Kalir for the donation of PCP. Correspondence and reprint requests should be addressed to A. M. Korczyn.     

Involvement of endorphins in the emotional behavior of pigs]

Social isolation and exposure to a new environment induce hyperactivity, vocalizations and ACTH release in weaned Piglets acutely submitted to this stress. These reactions are increased by pretreatment with morphine (0.5 and 1 mg/kg) and decreased by naloxone (1 mg/kg), suggesting that endogenous opiates modulate emotional behaviour in Pigs.     

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     

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.     

C-terminal fragment (residues 61–91) ofβ-lipotropin: Is it the natural opiate-like neurohormon of the brain?

Summary The C-terminal fragment of porcine -lipotropin (residues 61–91) has a very strong analgesic activity in vivo in rats. It is 20 times more potent than morphine if administered intracerebroventricularly (ICV) to rats. Its effect could be antagonized by naloxone. Presumably it is a natural opiate-like neurohormon of the brain.     

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.

---

---

Am 20. März 1976 gestorben.     

Evidence for an inhibitory role of beta-endorphin and other opioids on human total T rosette formation

Beta-endorphin, met-enkephalin, leu-enkephalin and morphine significantly inhibit rosette formation between human T lymphocytes and sheep red blood cells. This effect is completely reversed by naloxone, a specific antagonist, while naloxone by itself does not influence rosette formation. A further link between the immune system and the neuroendocrine system is suggested.     

Narcotic antagonism of seizures induced by a dopamine-derived tetrahydroisoquinoline alkaloid

This paper describes experiments designed to evaluate whether the narcotic antagonist naloxone significantly interferes with seizures induced by tetrahydroisoquinolines (TIQs). In these experiments we found that naloxone significantly reduced seizure scores induced by intra-cranially infusing mice with 50 micrograms of the dopamine-derived tetrahydroisoquinoline (TIQ) alkaloid, 6,7-dihydroxy TIQ. These findings support an opioid involvement in the actions of TIQs and may lead to further understanding of opioid-mediated novel excitatory receptors.     

D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 micrograms of D-ala2-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10(-3) M, 2 microliters), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.     

Stress by restraining potentiates morphine catalepsy in rats

Restraint-induced stress potentiated morphine catalepsy in rats. This potentiation was partially antagonized by pharmacologic treatments decreasing central serotonin, acetylcholine, prostaglandins and by naloxone. Selective increase in central dopamine also inhibited the potentiation.     

Ocular instillation of naloxone increases intraocular pressure in morphine-addicted patients: a possible test for detecting misuse of morphine

The effect of conjunctival instillation of naloxone on intraocular pressure has been examined in morphine-addicted patients as compared to non-addicted healthy volunteers. Morphine-addicted subjects showed a lower basal value of intraocular pressure as compared to the control volunteers. The instillation of naloxone caused a normalization of intraocular pressure to a level similar to that of control volunteers. This test seems to be a useful screening method for detecting morphine addiction.     

Ocular instillation of naloxone increases intraocular pressure in morphine-addicted patients: A possible test for detecting misuse of morphine

Summary The effect of conjunctival instillation of naloxone on intraocular pressure has been examined in morphine-addicted patients as compared to non-addicted healthy volunteers. Morphine-addicted subjects showed a lower basal value of intraocular pressure as compared to the control volunteers. The instillation of naloxone caused a normalization of intraocular pressure to a level similar to that of control volunteers. This test seems to be a useful screening method for detecting morphine addiction.     

The effects of naloxone on the analgesic activities of general anaesthetics

Summary Inhaled concentrations of nitrous oxide (80%), halothane (0.5%), trichloroethylene (0.5%) and s.c. ethanol (1 ml/kg) caused similar degrees of excitation and ataxia in mice. Nitrous oxide, tricholoroethylene and ethanol caused analgesia (hot plate and writhing tests), but only that caused by nitrous oxide was antagonized by naloxone (20 mg/kg). Halothane lacked analgesic activity.     

Arginine has a morphine-like action in insects

Summary Injections of arginine and morphine increased the voltage of electric shocks necessary to induce a defensive reaction in the Praying Mantis. The effect of both was inhibited by naloxone.We acknowledge the technical help of Alberto Meza and Alfonso Tablante and critical comments from Dr Carlo Caputo and Dr Erika Jaffe.     

Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats

CSF from a patient with congenital indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.     

Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats

Summary CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.