{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"DUTLYPZZJJBEAJ-QISMNGAHSA-N","prefName":"Hemopressin (Hp, PVNFKFLSH)","symbol":"Hémopressine","iupacName":null,"aliases":["Hemopressin","Hp","PVNFKFLSH","hémopressine de rat"],"cas":"568588-77-2","pubchemCid":"44560117","chebiId":null,"smiles":"CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]4CCCN4","molecularFormula":"C53H77N13O12","molecularWeight":1088.3,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/44560117"}},"classification":{"family":"endocannabinoide","familyLabel":"Endocannabinoid","origin":"natural","originLabel":"Naturel","structuralClassFr":"Nonapeptide linéaire correspondant aux résidus 95 à 103 de la chaîne alpha de l'hémoglobine. Il appartient à la famille des peptides dits pepcans, dont le membre le mieux caractérisé et le seul dont le caractère endogène soit établi est le dodécapeptide RVD-hémopressine (Pepcan-12), qui prolonge la même séquence de trois résidus du côté amino-terminal. Cette parenté de séquence est au cœur de la controverse : le nonapeptide peut être produit par clivage du dodécapeptide au cours de l'extraction."},"originSynthesis":{"heading":"Biosynthetic pathway (in vivo)","summaryFr":"Hemopressin corresponds to residues 95 to 103 of the alpha chain of haemoglobin, released by proteolytic cleavage. It is a peptide generation route, unrelated to the lipid route that produces anandamide or 2-AG from membrane phospholipids. The status of that cleavage is debated: it occurs, as documented, under acidic extraction conditions, which raises the possibility that the peptide is generated by the method rather than by the organism.","originNote":"A peptide fragment derived from haemoglobin, and not a lipid molecule like the classical endocannabinoids. Its endogenous nature is precisely the contested point: later work on the pepcan family indicates that the nonapeptide is a hydrolysis artefact produced under acidic conditions during sample preparation, and not a species genuinely present in tissues. The documented endogenous form is the longer peptide, RVD-hemopressin, described in this wiki under the name Pepcan-12.","discovered":"Le nonapeptide a été isolé au début des années 2000 dans le cerveau de rat, comme fragment de la chaîne alpha de l'hémoglobine libéré par action d'une endopeptidase, et nommé hémopressine en raison de son effet hypotenseur. Son rattachement au système endocannabinoïde vient de Heimann et collaborateurs, en 2007 : l'équipe montre qu'il se lie sélectivement au récepteur CB1 et s'y comporte en agoniste inverse, capable de bloquer la signalisation de ce récepteur sans toucher aux autres récepteurs couplés aux protéines G de la famille A, CB2 compris."},"pharmacology":{"summaryFr":"Hemopressin is a nonapeptide of sequence PVNFKFLSH, derived from the alpha chain of haemoglobin, which has held a singular place in the history of the endocannabinoid system: that of the first peptide ligand of the CB1 receptor. Heimann and colleagues (2007) established that it binds there selectively and behaves as an inverse agonist, blocking CB1 signalling without affecting the other G protein-coupled receptors of family A, CB2 included. Antinociceptive effects have been reported in animal models of inflammatory and neuropathic pain. That history nevertheless calls for an important caveat, and this wiki states it rather than passing over it: later work on the pepcan family indicates that this nonapeptide is a hydrolysis artefact generated under acidic conditions during sample preparation, and that it does not exist as such in tissues. The genuinely endogenous endocannabinoid peptide is the extended form, RVD-hemopressin or Pepcan-12, a negative allosteric modulator of CB1 and a positive one of CB2, which is the subject of a separate entry. Hemopressin therefore remains a documented pharmacological tool whose status as a physiological mediator is not settled.","receptorSummaryFr":"A selective inverse agonist of the CB1 receptor in the work of Heimann and colleagues (2007): it efficiently blocks CB1 signalling without acting on the other receptors of family A, including the closely related CB2. That selectivity makes it an interesting pharmacological tool. These results must nevertheless be read in the light of the later challenge to its endogenous existence: what is established is the activity of the administered peptide, not its physiological role.","binding":[{"target":"CB1","efficacy":"inverse_agonist","relativeActivity":55,"reported":null,"confidence":"low"}],"references":[{"label":"Heimann et coll. 2007 : l'hémopressine, agoniste inverse du récepteur CB1","pmid":"18077343","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/18077343/"},{"label":"Pepcan-12 (RVD-hémopressine), modulateur allostérique positif du CB2 (2017)","pmid":"28842619","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/28842619/"}]},"pharmacokinetics":"Peptide administré par voie parentérale ou orale dans les modèles animaux. Un effet antinociceptif a été rapporté après administration orale chez le rat, ce qui est notable pour un peptide de cette taille, généralement dégradé dans le tube digestif. Aucune donnée de pharmacocinétique humaine n'existe : biodisponibilité, distribution et demi-vie ne sont pas caractérisées chez l'humain.","metabolism":"Le devenir métabolique est celui d'un peptide court : hydrolyse par les peptidases plasmatiques et tissulaires en fragments plus petits puis en acides aminés libres. Le peptide est lui-même le produit d'une protéolyse de l'hémoglobine, ce qui le place à l'intersection du métabolisme des protéines et de la signalisation, et rend délicate la distinction entre production physiologique et dégradation.","detection":"Non recherché en toxicologie clinique ou médico-légale. Sa détection relève de la peptidomique par spectrométrie de masse, discipline où la question centrale reste précisément de distinguer un peptide réellement présent dans le tissu d'un fragment engendré par le protocole d'extraction, ce qui est l'enjeu de sa validité même.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":20},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":30},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":15},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":10},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":10}],"doseRanges":null,"humanDataCharacterised":true},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":false,"bannerTextFr":null,"toxicologyFr":"Aucune donnée de toxicologie humaine. Le peptide n'a jamais été administré à l'humain dans un cadre publié et ne circule pas comme produit de consommation. L'effet hypotenseur observé chez le rongeur, qui lui a valu son nom, constitue le principal effet pharmacologique à surveiller dans une éventuelle évaluation."},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":null,"reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"No harmonised control at Union level and no listing under the international conventions of 1961 and 1971. The peptide has not been the subject of any marketing authorisation application.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"No narcotic status: this is a peptide of biological origin, not listed in Annex IV of the arrêté of 22 February 1990 and with no circulation as a consumer product. It holds the status of a research reagent.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Heimann et coll. 2007 : l'hémopressine, agoniste inverse du récepteur CB1","pmid":"18077343","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/18077343/"},{"label":"Pepcan-12 (RVD-hémopressine), modulateur allostérique positif du CB2 (2017)","pmid":"28842619","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/28842619/"}],"meta":{"slug":"hemopressine","url":"https://en.phytogrammes.com/wiki/hemopressine","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-14","confidence":"medium","dataCompletenessPct":80,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}