Peripheral antinociceptive action of morphine and the synergistic interaction with Lamotrigine

Lamotrigine inhibits glutamate release through the preferential blockade of voltage-dependent Na+ channels. In contrast, morphine reduces release of excitatory amino acids through the activation of opioid receptors and also inhibits tetrodotoxin-resistant Na+ channels on peripheral afferent neurons....

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Bibliographic Details
Published in:Anesthesiology (Philadelphia) 2002-04, Vol.96 (4), p.921-925
Main Authors: ARGÜELLES, Carlos F, TORRES-LOPEZ, Jorge E, GRANADOS-SOTO, Vinicio
Format: Article
Language:English
Subjects:
Analgesics
Analgesics - pharmacology
Animals
Biological and medical sciences
Dose-Response Relationship, Drug
Drug Synergism
Excitatory Amino Acid Antagonists - pharmacology
Female
Lamotrigine
Male
Medical sciences
Morphine - pharmacology
Neuropharmacology
Pharmacology. Drug treatments
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Triazines - pharmacology
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Summary:Lamotrigine inhibits glutamate release through the preferential blockade of voltage-dependent Na+ channels. In contrast, morphine reduces release of excitatory amino acids through the activation of opioid receptors and also inhibits tetrodotoxin-resistant Na+ channels on peripheral afferent neurons. The current study was designed to investigate the antinociceptive effects of locally administered morphine and lamotrigine. The interaction between morphine and lamotrigine at the periphery was also examined. Morphine, lamotrigine, or a combination of morphine and lamotrigine was administered locally to female Wistar rats, and the antinociceptive effect was determined in the formalin test. Isobolographic analyses were used to define the nature of the functional interactions between morphine and lamotrigine. Peripheral administration of either morphine or lamotrigine produced a dose-related antinociceptive effect. Isobolographic analyses revealed that peripheral morphine and lamotrigine interacted synergistically in the formalin test. The study shows a functional interaction between lamotrigine and morphine at the peripheral level.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-200204000-00020