Effects of the combined continuous administration of morphine and the high-efficacy 5-HT1A agonist, F 13640 in a rat model of trigeminal neuropathic pain.
F 13640 is a recently discovered high-efficacy 5-HT1A receptor agonist that has demonstrated robust anti-allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5-HT1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5-HT1A receptor activation, and that the anti-allodynic effect that remained by the end of the two-week treatment period is due solely to 5-HT1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640.
Deseure
Kristof R
KR
Laboratory of Anesthesiology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. kristof.deseure@ua.ac.be
Adriaensen
Hugo F
HF
Colpaert
Francis C
FC
D000631:Aminopyridines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D015918:Infusion Pumps, Implantable; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014277:Trigeminal Neuralgia / Q000188:drug therapy*
D000631:Aminopyridines; D000701:Analgesics, Opioid; D009020:Morphine; D010880:Piperidines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D017366:Serotonin Receptor Agonists; C119079:3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methyl-6-methylaminopyridin-2-ylmethyl)amino)methyl)piperidin-1-yl)methanone; C473959:befiradol