Blockade of the polyamine site of NMDA receptors produces antinociception and enhances the effect of morphine, in mice

The possible effect of ifenprodil — a potent antagonist at the polyamine site of the NMDA receptor complex — on nociceptive threshold and morphine analgesia was investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection of ifenprodil significantly prolonged the reaction time o...

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Bibliographic Details
Published in:European journal of pharmacology 1996-02, Vol.298 (1), p.51-55
Main Authors: Bernardi, Mara, Bertolini, Alfio, Szczawinska, Krystyna, Genedani, Susanna
Format: Article
Language:English
Subjects:
Analgesia
Analgesics
Analgesics, Opioid - pharmacology
Animals
Biological and medical sciences
Calcium - metabolism
Excitatory Amino Acid Antagonists - pharmacology
Ifenprodil
Male
Medical sciences
Mice
Morphine
Morphine - pharmacology
Naloxone
Naloxone - pharmacology
Neuropharmacology
NMDA receptor
Pain
Pain Threshold - drug effects
Pharmacology. Drug treatments
Piperidines - pharmacology
Polyamine
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - physiology
α-MSH (α-melanocyte-stimulating hormone)
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Summary:The possible effect of ifenprodil — a potent antagonist at the polyamine site of the NMDA receptor complex — on nociceptive threshold and morphine analgesia was investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection of ifenprodil significantly prolonged the reaction time of mice at the dose of 30 mg/kg, and increased the analgesic effect of morphine. In the phenylquinone writhing test, ifenprodil reduced the number of abdominal constrictions of mice starting from the dose of 2.5 mg/kg i.p., and increased the effect of morphine. The effect of ifenprodil on pain threshold was prevented by naloxone. Moreover, ifenprodil antagonized the pain threshold-reducing effect of α-melanocyte-stimulating hormone (0.05 μg/mouse, intracerebroventricularly). These data show that blockade of the polyamine site of the NMDA receptor complex produces analgesia and increases the analgesic effect of morphine.
ISSN:0014-2999
1879-0712
DOI:10.1016/0014-2999(95)00778-4