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FMRFamide (Phe-Met-Arg-Phe) is a neuropeptide from a broad family of FMRFamide-related peptides (FaRPs) all sharing an -RFamide sequence at their C-terminus. First identified in Hard clam Mercenaria mercenaria it is thought to play an important role in cardiac activity regulation.[1] Several FMRFamid related peptides are known, regulating various cellular functions and possessing pharmacological actions, such as anti-opiate effects.[2] In Mercenaria mercenaria, FMRFamide has been isolated and demonstrated to increase both the force and frequency of the heartbeat through a biochemical pathway that is thought to involve the increase of cytoplasmic cAMP in the ventricular region (Higgins et al., 1978).

FMRFamide is an important neuropeptide in several phyla such as Insecta, Nematoda, Mollusca and Annelida.[3] It is the most abundant neuropeptide in endocrine cells of insect alimentary tracts along with allatostatin and tachykinin families, however the neuropeptide’s function is not known. Generally, the neuropeptide is encoded by several genes such as flp-1 through flp-22 in C. elegans. The common precursor of the FaRPs is modified to yield many different neuropeptides all having the same FMRFamide sequence. Moreover, these peptides are not functionally redundant.[4]

In invertebrates, the FMFRamide-related peptides are known to affect heart rate, blood pressure, gut motility, feeding behaviour and reproduction. In vertebrates such as mice, they are known to affect opioid receptors resulting in elicitation of naloxone-sensitive antinociception and reduction of morphine-induced antinociception.[5]


  1. López-Vera E, Aguilar MB, Heimer de la Cotera EP. (2008) FMRFamide and related peptides in the phylum mollusca. Peptides. 2008 Feb;29(2):310-7.
  2. Rőszer T, Bánfalvi G. (2011) FMRFamide-related peptides: Anti-opiate transmitters acting in apoptosis. Peptides. 2011 Apr 15.PMID:21524675
  3. Oetken M, Bachmann J, Schulte-Oehlmann U, Oehlmann J (2004). Evidence for endocrine disruption in invertebrates. Int. Rev. Cytol. 236: 1–44.
  4. Li C, Kim K, Nelson LS (November 1999). FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. Brain Res. 848 (1-2): 26–34.
  5. Raffa RB, Connelly CD (July 1992). Supraspinal antinociception produced by [D-Met2]-FMRFamide in mice. Neuropeptides 22 (3): 195–203.

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