The actions of FMRF-NH2 and FMRF-NH2 related peptides on mammals.

Since the initial isolation and characterization of FMRFamide (Phe-Met-Arg-Phe-NH2) from a molluscan source, the potential for the interaction of this neuropeptide with opioid systems has been suspected. Immunoreactive FMRFamide-like material is found in mammals (particularly in brain, spinal cord and GI tract) and mammalian-derived FMRFamide-related peptides (FaRPs) have been identified. A considerable amount of data supports the hypothesis that FMRFamide or mammalian FaRPs function as endogenous antiopiates, particularly with regard to opioid-induced antinociception and other opioid-induced behaviors. They have also been reported to be capable of altering the rate of morphine tolerance development and precipitating withdrawal in morphine-dependent animals. These data imply that FMRFamide or FaRPs are competitive antagonists at opiate receptors. The relatively low affinity for opiate receptors also suggests other possibilities, including mammalian FMRFamide (or FaRP) receptors equivalent to those in invertebrates, partial agonism at opiate receptors or, an indirect (modulatory) role. Whatever the actual mechanism, FMRFamide-like peptides and other 'anti-opiate' peptides might have critical roles in the development of opioid tolerance and dependence or in the pharmacologic study or clinical treatment of these phenomena.