{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"QJDNHGXNNRLIGA-DOFZRALJSA-N","prefName":"N-arachidonoylserotonin","symbol":"AA-5-HT","iupacName":null,"aliases":["AA-5-HT","N-arachidonoyl serotonin","arachidonoyl sérotonine","AA-5HT"],"cas":"187947-37-1","pubchemCid":"10027372","chebiId":null,"smiles":"CCCCC/C=C\\C/C=C\\C/C=C\\C/C=C\\CCCC(=O)NCCC1=CNC2=C1C=C(C=C2)O","molecularFormula":"C30H42N2O2","molecularWeight":462.7,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/10027372"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"N-acylsérotonine : conjugué amide de l'acide arachidonique et de la sérotonine. La partie acyle est celle de l'anandamide, ce qui explique la reconnaissance par le site actif de la FAAH et le comportement d'inhibiteur ; la partie sérotonine apporte le noyau indolique responsable de l'interaction avec le TRPV1. La molécule illustre une stratégie de conception explicite, l'assemblage de deux pharmacophores connus pour obtenir une double activité dans une seule entité."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"No plant biosynthetic route. The molecule joins by an amide bond the twenty-carbon polyunsaturated chain of arachidonic acid and the indole core of serotonin. It belongs to the N-acylserotonin class, described here by chemical class only.","originNote":"A synthetic compound, designed in the laboratory by formal conjugation of arachidonic acid and serotonin. It is used as a pharmacological tool and as a lead structure for the design of dual-mechanism analgesics, with no authorised human use and no circulation as a consumer product.","discovered":"Conçue à la fin des années 1990 comme inhibiteur de l'hydrolase des amides d'acides gras, la FAAH, l'enzyme qui dégrade l'anandamide. Sa seconde propriété a été établie par Maione et collaborateurs en 2007 : la molécule antagonise également le canal TRPV1, récepteur de la capsaïcine. Cette double action, sur une enzyme du versant cannabinoïde et sur un canal du versant vanilloïde, en a fait un outil de référence pour interroger le point de rencontre entre les deux systèmes."},"pharmacology":{"summaryFr":"N-arachidonoylserotonin is a mixed blocker of the endocannabinoid and endovanilloid systems, widely used as a pharmacological tool. It inhibits FAAH, the hydrolase that degrades anandamide, and antagonises the TRPV1 channel. Maione and colleagues (2007) established that second aspect on HEK-293 cells expressing recombinant rat or human TRPV1, with an IC50 of 37 to 40 nM against 100 nM capsaicin, and showed marked analgesic activity in several pain models in rats and mice, from the formalin test to chronic constriction of the sciatic nerve. Dissection of the mechanism is instructive: the effect is partly lifted by AM251, a CB1 antagonist, which confirms passage through the elevation of anandamide and indirect activation of CB1; it is also reproduced by TRPV1 antagonists given alone, and lifted by them, which confirms the vanilloid component. That dual activity explains its efficacy on acute pain as on chronic peripheral pain. Anxiolytic-type effects and an action on contextual fear memory have also been reported.","receptorSummaryFr":"A dual mechanism. On the one hand, inhibition of FAAH, which raises tissue anandamide levels and therefore indirectly activates CB1 receptors: the analgesic effect is lifted by AM251, a CB1 antagonist, which demonstrates the passage through that route. On the other hand, direct antagonism of the TRPV1 channel, with an IC50 of 37 to 40 nM against 100 nM capsaicin, at the recombinant rat receptor as at the human one. The molecule thus acts either by desensitisation of TRPV1 consequent on the elevation of anandamide, or as a direct antagonist of that channel.","binding":[{"target":"FAAH","efficacy":"antagonist","relativeActivity":75,"reported":null,"confidence":"low"},{"target":"TRPV1","efficacy":"antagonist","relativeActivity":78,"reported":"CI50 de 37 à 40 nM contre 100 nM de capsaïcine (TRPV1 recombinant de rat et humain, Maione 2007)","confidence":"medium"},{"target":"CB1","efficacy":"modulator","relativeActivity":40,"reported":null,"confidence":"low"}],"references":[{"label":"Maione et coll. 2007 : actions analgésiques de la N-arachidonoylsérotonine, FAAH et TRPV1","pmid":"17279090","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17279090/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique humaine : la molécule n'a pas fait l'objet de développement clinique. Chez le rongeur, elle est active par voie systémique et par administration locale intracérébrale, notamment dans la substance grise périaqueducale et la moelle ventromédiane rostrale, structures par lesquelles passe une partie de son effet analgésique.","metabolism":"Le métabolisme humain n'est pas caractérisé. La liaison amide constitue le point de fragilité attendu, avec une hydrolyse libérant acide arachidonique et sérotonine ; la molécule étant elle-même un inhibiteur de la FAAH, elle est relativement protégée de la voie d'hydrolyse principale des amides d'acides gras, ce qui participe de sa durée d'action.","detection":"Aucun dépistage de routine ne le cible. Sa quantification en recherche passe par la chromatographie liquide couplée à la spectrométrie de masse en tandem, généralement dans le même protocole lipidomique que celui qui dose l'anandamide et le 2-AG, dont il fait varier les niveaux.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":60},{"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":35},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":20},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":25}],"doseRanges":null,"humanDataCharacterised":true},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":false,"bannerTextFr":null,"toxicologyFr":"Aucune donnée de toxicologie humaine, aucune exposition humaine documentée. Chez l'animal, les doses analgésiques sont bien tolérées dans les études publiées. Le blocage du TRPV1 appelle en théorie la même vigilance que pour les autres antagonistes de ce canal, notamment sur la thermorégulation et sur la perception des températures nocives, point non caractérisé pour ce composé."},"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 compound holds the status of a laboratory reagent.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"A research compound, not listed in Annex IV of the arrêté of 22 February 1990 and not covered by the generic clauses targeting synthetic cannabinoids, which concern indole, indazole or related skeletons bearing alkyl chains. No human use is authorised and the molecule does not circulate as a consumer product.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Maione et coll. 2007 : actions analgésiques de la N-arachidonoylsérotonine, FAAH et TRPV1","pmid":"17279090","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/17279090/"}],"meta":{"slug":"aa-5-ht","url":"https://en.phytogrammes.com/wiki/aa-5-ht","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."}}