Supraspinal antinociception produced by [D-Met2]-FMRFamide in mice.
The ability of Phe-Met-Arg-Phe-NH2 (FMRFamide) or [D-Met2]-FMRFamide to produce antinociception in mice, or to block morphine-induced antinociception, was examined using the tail-flick and tail-immersion (55 degrees C) tests. [D-Met2]-FMRFamide dose-dependently produced antinociception following intracerebroventricular (i.c.v.) administration with ED50 values (95% confidence limits) of 5.0 (2.2-7.2) and 12.8 (8.1-19.9) micrograms in the tail-flick and tail-immersion tests, respectively. FMRFamide did not produce a maximal effect in the tail-flick test. Naloxone (administered s.c. 20 min prior to the i.c.v. administration of [D-Met2]-FMRFamide) dose-dependently attenuated [D-Met2]-FMRFamide-induced antinociception. The shift in the [D-Met2]-FMRFamide dose-response curve was parallel and a pA2 value for naloxone of 6.3 +/- 0.3 was determined from a Schild plot analysis. Mice made tolerant to the antinociceptive effect of morphine were cross-tolerant to the antinociceptive effect of [D-Met2]-FMRFamide. FMRFamide and [D-Met2]-FMRFamide both produced rightward, parallel shifts of the morphine antinociceptive dose-response curve. The findings that [D-Met2]-FMRFamide both elicited naloxone-sensitive antinociception and attenuated morphine-induced antinociception are consistent with the view that FMRFamide-related peptides (FaRPs) are weak agonists at opioid receptors and, further, appear to reconcile the apparently chimeric agonist and antagonist properties of these peptides observed in vivo.
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Drug Discovery Research, The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Connelly
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D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D019835:FMRFamide; D006358:Hot Temperature; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010465:Perception / Q000187:drug effects; D011312:Pressure; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D013623:Tail
D000700:Analgesics; D009479:Neuropeptides; D011957:Receptors, Opioid; D009270:Naloxone; D019835:FMRFamide; D009020:Morphine