{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"GZNIYOXWFCDBBJ-UHFFFAOYSA-N","prefName":"LY-2183240","symbol":"LY-2183240","iupacName":"N,N-diméthyl-5-[(4-phénylphényl)méthyl]tétrazole-1-carboxamide","aliases":["LY2183240","LY 2183240"],"cas":"874902-19-9","pubchemCid":"11507802","chebiId":null,"smiles":"CN(C)C(=O)N1C(=NN=N1)CC2=CC=C(C=C2)C3=CC=CC=C3","molecularFormula":"C17H17N5O","molecularWeight":307.35,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/11507802"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Carbamoyl-tétrazole, sous-classe des urées hétérocycliques. La molécule associe un tétrazole, cycle à quatre azotes, portant en position 1 une fonction diméthylcarboxamide et en position 5 un groupement biphénylméthyle. Le mécanisme d'inhibition découle directement de cet agencement : la sérine catalytique de l'enzyme attaque le carbonyle du carboxamide, le tétrazole part comme groupe partant, et l'enzyme reste carbamylée donc inactive. Cette réactivité est intrinsèque au chémotype et explique la promiscuité observée vis-à-vis d'autres hydrolases à sérine."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule is a heterocyclic urea: a tetrazole core bears on one side a biphenylmethyl group and on the other a dimethylcarboxamide function. It is that tetrazole-carboxamide sequence which constitutes the reactive group, the tetrazole playing the role of leaving group in the reaction with the enzyme.","originNote":"A wholly synthetic compound with no natural occurrence. It is produced as a pharmacological research reagent and has never been the subject of clinical development.","discovered":"Introduit dans la littérature comme bloqueur du transporteur présumé de l'anandamide, capable de perturber la captation cellulaire de cet endocannabinoïde et de produire une analgésie chez l'animal. Sa véritable nature a été établie en 2006 par Alexander et Cravatt, à l'institut Skaggs du Scripps Research Institute, dont le travail a réorienté l'interprétation de tous les résultats obtenus avec lui."},"pharmacology":{"summaryFr":"LY-2183240 illustrates the commonest risk of experimental pharmacology: that of drawing a conclusion about a mechanism from a tool whose target one believes one knows. The compound had been introduced as an inhibitor of the presumed anandamide transporter, and the fact that it reduced the cellular uptake of that endocannabinoid while producing analgesia was read as an argument in favour of the existence of such a transporter. Alexander and Cravatt showed in 2006 that it is in reality a potent covalent inhibitor of fatty acid amide hydrolase, the enzyme that hydrolyses anandamide, and that it inactivates it by carbamylation of the nucleophilic serine of its active site. The interpretive consequence is direct: the blockade of uptake observed with this compound is explained by inactivation of the enzyme, which on the contrary provides an argument in favour of the competing model, the one in which enzymatic hydrolysis constitutes the metabolic engine that sustains the diffusion of anandamide into the cell. The screening by activity-based proteomic probes carried out in the same study moreover revealed that the molecule inhibits several other serine hydrolases of the brain, which led the authors to warn against this heterocyclic urea chemotype, whose reactivity towards the proteome appears excessive for pharmaceutical development. The compound retains a historical value in the long-open debate on the existence of a membrane transporter for anandamide.","receptorSummaryFr":"A potent covalent inhibitor of fatty acid amide hydrolase, which it inactivates by carbamylation of the nucleophilic serine residue of the active site. Alexander and Cravatt established that it is that inhibition, and not a blockade of transport, which accounts for the compound's effect on the cellular uptake of anandamide. Their screening by activity-based proteomic probes moreover identified several other brain serine hydrolases inhibited by the molecule, which led them to characterise this heterocyclic urea chemotype as of potentially excessive reactivity for drug design. The compound has no described direct action on cannabinoid receptors.","binding":[{"target":"FAAH","efficacy":"antagonist","relativeActivity":90,"reported":"Inhibition covalente par carbamylation de la sérine nucléophile","confidence":"medium"},{"target":"Transporteur membranaire de l'anandamide","efficacy":"modulator","relativeActivity":20,"reported":"Effet attribué à tort au transport ; expliqué par l'inhibition de la FAAH","confidence":"medium"}],"references":[{"label":"Alexander et Cravatt 2006 : le LY2183240, prétendu bloqueur du transport endocannabinoïde, est un inhibiteur de la FAAH et d'autres hydrolases","pmid":"16866524","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16866524/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique détaillée n'est publiée. Les travaux disponibles portent sur des essais in vitro et sur l'administration chez le rongeur dans des modèles d'antinociception. Aucune dose humaine n'est caractérisée et le composé n'a jamais été administré à l'humain.","metabolism":"Aucune étude de métabolisme n'est publiée. Le composé se consomme en carbamylant les hydrolases à sérine qu'il rencontre, mécanisme qui constitue à la fois son action et sa voie de disparition, et la restauration de l'activité enzymatique dépend de la resynthèse protéique.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. L'évaluation de son action passe par le profilage d'activité des hydrolases à sérine, technique qui mesure l'occupation des sites actifs sur l'ensemble du protéome plutôt que la molécule elle-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":5},{"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":15},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":10}],"doseRanges":null,"humanDataCharacterised":false},"indications":{"approvedMedicines":[]},"harmProfile":{"unstudiedBanner":true,"bannerTextFr":"Aucune dose humaine caractérisée : données animales / in vitro uniquement. Profil d'effet, marge de sécurité et toxicité aiguë non documentés en clinique humaine.","toxicologyFr":"Aucune donnée de toxicologie humaine n'est disponible et aucune dose humaine n'est caractérisée. Le point de vigilance identifié par les auteurs eux-mêmes est la promiscuité de cible : l'inhibition de plusieurs hydrolases à sérine cérébrales autres que l'enzyme visée rend imprévisibles les conséquences d'une administration et disqualifie le chémotype pour un usage thérapeutique."},"legal":{"scheduleStatus":"unscheduled","scheduleLabel":"Unscheduled","frScheduleStatus":"unscheduled","tiers":[{"jurisdiction":"international","jurisdictionLabel":"International","label":"Non inscrit aux conventions de contrôle","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"eu","jurisdictionLabel":"Union européenne","label":"Réactif de recherche ; non contrôlé","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Non inscrit ; usage de laboratoire uniquement","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"Alexander et Cravatt 2006 : le LY2183240, prétendu bloqueur du transport endocannabinoïde, est un inhibiteur de la FAAH et d'autres hydrolases","pmid":"16866524","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/16866524/"}],"meta":{"slug":"ly-2183240","url":"https://en.phytogrammes.com/wiki/ly-2183240","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-16","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}