title: Peripheral antinociceptive action of morphine and the synergistic interaction with lamotrigine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The study shows a functional interaction between lamotrigine and morphine at the peripheral level.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Granjas Coapa, Mexico.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Argüelles
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Torres-López
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D000077213:Lamotrigine; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014227:Triazines; D009020:Morphine; D000077213:Lamotrigine