{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"BJSDNVVWJYDOLK-UHFFFAOYSA-N","prefName":"BML-190 (indomethacin morpholinylamide)","symbol":"BML-190","iupacName":"2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-1-morpholin-4-ylethanone","aliases":["BML190","Indomethacin morpholinylamide","IMMA"],"cas":"2854-32-2","pubchemCid":"2415","chebiId":"93649","smiles":"CC1=C(C2=C(N1C(=O)C3=CC=C(C=C3)Cl)C=CC(=C2)OC)CC(=O)N4CCOCC4","molecularFormula":"C23H23ClN2O4","molecularWeight":426.135,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/2415","chebi":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:93649"}},"classification":{"family":"ecs_tool","familyLabel":"ECS modulator (research)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Amide de morpholine dérivé de l'indométacine, chémotype d'aryl-indole acétamide. Le noyau indole porte un méthoxyle, un méthyle et un chlorobenzoyle sur son azote, exactement comme dans la molécule mère, seule la fonction terminale changeant : l'acide acétique de l'indométacine devient ici un acétamide de morpholine. Cette substitution supprime la charge négative portée par le carboxylate à pH physiologique, charge indispensable à l'inhibition des cyclooxygénases mais incompatible avec le site de liaison lipophile du récepteur CB2."},"originSynthesis":{"heading":"Origin (research tool)","summaryFr":"An entirely chemical route, described here by class only. The molecule derives from indomethacin by transformation of its carboxylic acid function into a morpholine amide. The rest of the skeleton is preserved: a methoxylated and methylated indole core, acylated on its nitrogen by a chlorobenzoyl. That modification of a single function tips the molecule from the profile of a cyclooxygenase inhibitor towards that of a CB2 receptor ligand.","originNote":"A wholly synthetic compound, derived from an existing medicine. It is produced as a pharmacology reagent and has not been the subject of clinical development of its own.","discovered":"Dérivé de l'indométacine, anti-inflammatoire non stéroïdien ancien, obtenu en remplaçant sa fonction acide carboxylique par un amide de morpholine. Son comportement au récepteur CB2 a été caractérisé en 2003 par New et Wong, à l'université des sciences et technologies de Hong Kong, qui ont établi qu'il s'agit d'un agoniste inverse et non d'un simple ligand."},"pharmacology":{"summaryFr":"BML-190 illustrates how a minimal chemical modification can redirect a molecule towards an entirely different target. Indomethacin is a non-steroidal anti-inflammatory known since the 1960s, whose activity rests on the inhibition of cyclooxygenases by its carboxylic acid function. Turning that acid into a morpholine amide removes that activity and brings out an affinity for the cannabinoid CB2 receptor. New and Wong clarified in 2003 the nature of that interaction, a question not resolved by the measurement of an affinity alone. A ligand may activate a receptor, block it without more, or reduce the activity the receptor exerts spontaneously in the absence of any agonist; that last behaviour, inverse agonism, is revealed only in systems where such constitutive activity is measurable. The authors worked on cells expressing the human CB2 receptor abundantly and observed that the compound potentiates the accumulation of cyclic AMP induced by forskolin, the exact opposite of the effect of an agonist, and that it lowers the basal production of inositol phosphates when the receptor is coupled to a chimeric G protein. The compound therefore acts on two families of signalling pathways. Its reach is that of a tool: it makes it possible to demonstrate that the CB2 receptor possesses spontaneous activity and to quantify it. Its metabolism has moreover been characterised on rat liver microsomes, where at least fifteen products were identified, which makes it one of the few laboratory CB2 ligands whose metabolic fate has been described.","receptorSummaryFr":"An inverse agonist of the human CB2 receptor. New and Wong show in 2003 that the compound, on HEK-293 cells stably expressing the human CB2 receptor, potentiates the accumulation of cyclic AMP stimulated by forskolin, meaning that it produces the opposite of the effect of an agonist, and that it lowers the basal production of inositol phosphates when the receptor is coupled to a chimeric G protein. The compound therefore acts on pathways coupled to G proteins of the Gi/o and Gq families. That profile, shared in the same work by AM251 at the CB1 receptor, makes it a tool for revealing the constitutive activity of the CB2 receptor, that is its spontaneous signalling in the absence of any agonist.","binding":[{"target":"CB2","efficacy":"inverse_agonist","relativeActivity":70,"reported":"Agoniste inverse : potentialise l'AMP cyclique stimulée par la forskoline et abaisse les inositol phosphates basaux (New et Wong 2003)","confidence":"medium"},{"target":"CB1","efficacy":"modulator","relativeActivity":8,"reported":"Ligand décrit comme sélectif du CB2 ; pas d'action rapportée au CB1","confidence":"medium"}],"references":[{"label":"New et Wong 2003 : le BML-190 et l'AM251 agissent en agonistes inverses au récepteur CB2 humain, signalisation par l'AMP cyclique et les inositol phosphates","pmid":"12586356","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/12586356/"},{"label":"Zhang et coll. 2010 : métabolisme in vitro de l'indométacine morpholinylamide sur microsomes hépatiques de rat","pmid":"20542112","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/20542112/"}]},"pharmacokinetics":"Aucune donnée de pharmacocinétique in vivo n'est publiée pour ce composé, employé comme outil sur systèmes cellulaires. Aucune donnée humaine n'existe et aucune dose humaine n'est caractérisée.","metabolism":"Le métabolisme a été caractérisé in vitro sur microsomes hépatiques de rat par Zhang et collaborateurs en 2010. Au moins quinze produits ont été identifiés par chromatographie liquide couplée à la spectrométrie de masse en tandem, rattachés à quatre voies principales de phase 1 agissant seules ou en combinaison : la perte du groupement chlorobenzyle, l'hydroxylation sur le noyau indole ou sur le cycle morpholine, l'ouverture du cycle morpholine, et la déméthylation du méthoxyle porté par l'indole.","detection":"La molécule ne figure dans aucun panel de dépistage et n'a pas d'intérêt médicolégal. Son dosage et celui de ses métabolites relèvent de la chromatographie liquide couplée à la spectrométrie de masse en tandem, méthode employée dans l'étude de métabolisme in vitro publiée.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":10},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":10},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":8},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":5},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":5}],"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 publiée pour ce composé et aucune dose humaine n'est caractérisée. La molécule dont il dérive, l'indométacine, possède un profil de toxicité digestive et rénale bien documenté, mais celui-ci est lié à l'inhibition des cyclooxygénases, activité que la modification chimique supprime : il ne peut donc pas être transposé au dérivé."},"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":"New et Wong 2003 : le BML-190 et l'AM251 agissent en agonistes inverses au récepteur CB2 humain, signalisation par l'AMP cyclique et les inositol phosphates","pmid":"12586356","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/12586356/"},{"label":"Zhang et coll. 2010 : métabolisme in vitro de l'indométacine morpholinylamide sur microsomes hépatiques de rat","pmid":"20542112","doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/20542112/"}],"meta":{"slug":"bml-190","url":"https://en.phytogrammes.com/wiki/bml-190","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-17","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}