{"schemaVersion":"cwiki-fiche-1.0","identifiers":{"inchiKey":"MEUQWHZOUDZXHH-UHFFFAOYSA-N","prefName":"Pravadoline (WIN 48098)","symbol":"Pravadoline","iupacName":"(4-methoxyphenyl)-[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]methanone","aliases":["WIN 48098","WIN 48098-6","pravadoline maleate","BRL-38227"],"cas":"92623-83-1","pubchemCid":"56463","chebiId":null,"smiles":"CC1=C(C2=CC=CC=C2N1CCN3CCOCC3)C(=O)C4=CC=C(C=C4)OC","molecularFormula":"C23H26N2O3","molecularWeight":378.5,"xrefs":{"pubchem":"https://pubchem.ncbi.nlm.nih.gov/compound/56463"}},"classification":{"family":"scra","familyLabel":"Synthetic cannabinoid (SCRA)","origin":"synthetic","originLabel":"Synthétique","structuralClassFr":"Aminoalkylindole, prototype de la classe. Le noyau indole porte une chaîne 2-(morpholin-4-yl)éthyle sur l'azote en position 1, un méthyle en position 2, et une cétone aroyle en position 3 reliée à un 4-méthoxyphényle. Le remplacement ultérieur de cette tête méthoxyphényle par un naphtalène a donné les naphtoylindoles, dont le JWH-018 : toute la nomenclature moderne des cannabinoïdes de synthèse à cœur indole descend de ce squelette."},"originSynthesis":{"heading":"Origin (pharmaceutical research → illicit market)","summaryFr":"No biological route. Pravadoline is an aminoalkylindole obtained by synthesis: an indole core bears at position 1 a morpholinoethyl chain, at position 2 a methyl, and at position 3 a ketone function linking a 4-methoxyphenyl ring. It is described here by chemical class only.","originNote":"A wholly synthetic molecule, absent from cannabis as from any living organism. It was designed within a pharmaceutical programme and has no significant presence on the consumer product market; its chemical progeny, by contrast, has spread far beyond the laboratory.","discovered":"Développée dans les années 1980 par le groupe de recherche Sterling comme anti-inflammatoire non stéroïdien inhibiteur de la synthèse des prostaglandines, la pravadoline est à l'origine d'une découverte accidentelle majeure. Son effet analgésique apparaissait à des doses dix fois inférieures à la dose anti-inflammatoire efficace, écart inexplicable par la seule inhibition de la cyclooxygénase, et il n'était pas levé par la naloxone, ce qui excluait une action opioïde. L'explication est venue de la pharmacologie cannabinoïde : la pravadoline s'est révélée être le premier représentant d'une classe entièrement nouvelle d'agonistes des récepteurs cannabinoïdes, les aminoalkylindoles."},"pharmacology":{"summaryFr":"Pravadoline (WIN 48098) is the founding molecule of the aminoalkylindoles, and thereby of the entire lineage of indole-cored synthetic cannabinoids. Designed by the Sterling group in the 1980s as a non-steroidal anti-inflammatory related to indomethacin, it did indeed inhibit prostaglandin synthesis. The anomaly lay in its analgesic effect, obtained at doses ten times lower than the anti-inflammatory dose and insensitive to naloxone: neither cyclooxygenase nor opioid receptors could account for it. Pravadoline proved to be an agonist of cannabinoid receptors, the first of a then unknown chemical class. Optimisation of the series subsequently dissociated the two activities, the effect on prostaglandins fading as CB1 activity strengthened, and led to WIN 55,212-2, a reference agonist still used today, then to the JWH series that fed the fake cannabis market. Clinical development of pravadoline itself was abandoned.","receptorSummaryFr":"A cannabinoid receptor agonist, of modest potency compared with its progeny. The antinociceptive activity of the aminoalkylindole series was traced to action at the CB1 receptor; as the analogues were optimised, their capacity to block prostaglandin synthesis faded while cannabinoid activity strengthened, which confirmed that the two effects arose from distinct mechanisms. Pravadoline moreover retains a cyclooxygenase inhibitory activity, with inhibition of prostaglandin synthesis in the mouse brain.","binding":[{"target":"CB1","efficacy":"full_agonist","relativeActivity":35,"reported":null,"confidence":"low"},{"target":"COX","efficacy":"antagonist","relativeActivity":40,"reported":null,"confidence":"low"}],"references":[{"label":"PubChem CID 56463 : pravadoline, identifiants et propriétés","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/56463"},{"label":"The Spicy Story of Cannabimimetic Indoles (revue, Molecules 2021)","pmid":null,"doi":null,"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538531/"}]},"pharmacokinetics":"La molécule a été évaluée par voie orale chez l'animal, avec une inhibition de la synthèse des prostaglandines mesurable ex vivo après administration orale. Elle a fait l'objet d'un développement clinique comme antalgique, abandonné depuis, et aucun profil pharmacocinétique humain de référence n'est aujourd'hui publiquement documenté sous une forme exploitable.","metabolism":"Le métabolisme humain de la pravadoline n'est pas caractérisé dans la littérature accessible. La structure offre plusieurs sites d'attaque attendus, dont la O-déméthylation du groupement méthoxy et l'oxydation du cycle morpholine, mais ces voies relèvent de l'attente de classe et non d'une observation publiée pour ce composé.","detection":"La pravadoline n'est pas recherchée en toxicologie de routine et n'est pas détectée par les immunoessais cannabis. Elle sert surtout de référence chromatographique dans les bibliothèques spectrales des laboratoires travaillant sur la série des aminoalkylindoles, où elle marque l'origine structurale de la famille.","subjectiveEffects":{"profile":[{"key":"calm","label":"Calm","description":"Relaxation of body and mind; reduced mental noise without marked drowsiness.","intensity":35},{"key":"focus","label":"Clarity","description":"Sustained attention and clear thinking; functional lucidity, not euphoria.","intensity":20},{"key":"sleep","label":"Sleep","description":"Sedative effect: aids sleep onset and the continuity of deep sleep.","intensity":30},{"key":"appetite","label":"Appetite","description":"Stimulation of hunger and of taste appreciation (the “munchies” effect).","intensity":25},{"key":"uplift","label":"High","description":"Euphoria and sensory intensity; altered perception of time and space.","intensity":25}],"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":"Aucun signalement d'intoxication n'est associé à la pravadoline elle-même, qui n'a pas circulé comme produit de consommation. Son intérêt est historique et pharmacologique. Le risque réel de la classe qu'elle a inaugurée est porté par ses descendants optimisés, agonistes complets de très haute affinité responsables de la morbidité observée avec les faux cannabis."},"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. Clinical development of the molecule as an analgesic was abandoned and it never obtained a marketing authorisation in a Member State.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null},{"jurisdiction":"fr","jurisdictionLabel":"France","label":"Pravadoline is not listed by name in Annex IV of the arrêté of 22 February 1990. Its structure, an indole ketone bearing an aminoalkyl chain and a methoxyphenyl head, does not correspond to the naphthoylindole families or to the carboxamide families added by the arrêté of 31 March 2017. In practice it holds the status of a research compound, with no authorised human use and no commercialisation.","reference":null,"url":null,"effectiveDate":null,"lastVerified":"2026-05-01","supersededBy":null}],"sourcesFr":"EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA."},"references":[{"label":"PubChem CID 56463 : pravadoline, identifiants et propriétés","pmid":null,"doi":null,"url":"https://pubchem.ncbi.nlm.nih.gov/compound/56463"},{"label":"The Spicy Story of Cannabimimetic Indoles (revue, Molecules 2021)","pmid":null,"doi":null,"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538531/"}],"meta":{"slug":"pravadoline","url":"https://en.phytogrammes.com/wiki/pravadoline","lastVerified":"2026-05-01","dataUpdatedAt":"2026-08-14","confidence":"medium","dataCompletenessPct":90,"disclaimerFr":"Contenu éditorial informatif, sans valeur d'avis médical ni juridique. Sources primaires citées par fiche. Réservé aux adultes."}}