MonlunabantMonlunabant (INV-202)

Formula

C₂₆H₂₂ClF₃N₆O₃S

Molar mass

591.00 g·mol⁻¹

CAS

2712480-46-9

PubChem CID

164888943

Origin

A wholly synthetic compound with no natural occurrence. It is produced within pharmaceutical development and is not commercialised.

InChIKey

GYJPQNPVIJXXTA-JOCHJYFZSA-N

Editorial estimate, not clinical.

Monlunabant is an inverse agonist of the CB1 receptor designed to act peripherally. It answers a question posed by the failure of rimonabant, withdrawn from the European market in 2008 for depression and suicidal ideation: does the metabolic benefit of CB1 blockade come from peripheral receptors, in which case a molecule that does not enter the brain could retain it without the risk? The phase 2a trial published in 2025 by Knop and colleagues brings elements in both directions. Conducted over sixteen weeks in 243 obese adults with metabolic syndrome, it measured at week 16 weight differences against placebo of 6.4 kilograms for 10 milligrams, 6.9 kilograms for 20 milligrams and 8.0 kilograms for 50 milligrams: efficacy is real and clinically significant. But the adverse effects, essentially gastrointestinal and psychiatric, followed the dose, and above all discontinuations for adverse events reached 13, 27 and 42 per cent according to dose against none under placebo, driven by nausea, anxiety, diarrhoea, irritability and sleep disturbance. The authors conclude that the gain at high doses is small relative to that cost and that lower doses must be assessed. The preclinical work of Mullassaril and colleagues points the same way by contesting the premise: in mice, appetite suppression and blockade of agonist-induced hypothermia appear at the same doses, which points to central receptors, whereas doses saturating peripheral receptors alone remained without effect on appetite.

An entirely chemical route, described here by class only. The molecule retains the pyrazoline core characteristic of the rimonabant lineage, bearing a chlorophenyl and a phenyl, but adds to it a strongly polar sulfonyl-acylguanidine assembly linked to a trifluoromethylphenyl. It is that polar portion which aims to restrict passage of the blood-brain barrier.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

ECS modulator (research)

Origin

A wholly synthetic compound with no natural occurrence. It is produced within pharmaceutical development and is not commercialised.

Status

Unscheduled

1. 1.Knop et coll. 2025 : efficacité et sécurité du monlunabant dans l'obésité avec syndrome métabolique, essai de phase 2aPMID 41038215
2. 2.Mullassaril et coll. 2025 : le monlunabant supprime l'appétit par un mécanisme centralPMID 39969070