DrinabantDrinabant (AVE1625)

Formula

C₂₃H₂₀Cl₂F₂N₂O₂S

Molar mass

497.40 g·mol⁻¹

CAS

358970-97-5

PubChem CID

10278470

Origin

A wholly synthetic compound with no natural occurrence. It was designed as a drug candidate and never reached the market; its production belongs to the laboratory and to clinical research.

InChIKey

IQQBRKLVEALROM-UHFFFAOYSA-N

Editorial estimate, not clinical.

Drinabant, known under the code AVE1625, is a CB1 receptor antagonist developed by Sanofi-Aventis at the time when industry was exploring that target for obesity, smoking cessation and cognitive disorders. Its place in the literature rests on the quality of its clinical demonstration of mechanism. Zuurman and colleagues used Δ9-THC as a pharmacological probe: given to volunteers, it produces a set of measurable effects, feeling of euphoria, altered perception, body sway, accelerated heart rate. From 20 milligrams, the compound inhibited most of those responses, without itself producing the slightest psychological or behavioural effect or modifying heart rate. That result establishes that it crosses the blood-brain barrier and occupies the central receptor. In animal pharmacology, the compound showed a profile distinct from that of its competitors. It acts on metabolic parameters independently of the reduction in food intake in rats, and it was studied as an adjunct to antipsychotics: Black and colleagues reported that it corrects latent inhibition deficits and improves working and episodic memory in rodents, without reducing the efficacy of the antipsychotics, while diminishing the catalepsy and weight gain they induce. They also stress that, unlike other CB1 antagonists, it did not produce an anxiogenic-type effect. Development did not succeed, in a context where the withdrawal of rimonabant in 2008 for psychiatric risk lastingly compromised the class.

An entirely chemical route, described here by class only. The molecule combines a central azetidine ring, bearing a bis(4-chlorophenyl)methyl group on the nitrogen, with a methanesulfonamide function linked to a difluorophenyl core. It thus breaks with the pyrazole skeleton of rimonabant while retaining the diarylmethyl motif characteristic of the antagonists of that generation.

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 was designed as a drug candidate and never reached the market; its production belongs to the laboratory and to clinical research.

Status

Unscheduled

1. 1.Zuurman et coll. 2010 : inhibition par l'AVE1625 des effets centraux et cardiaques du THC chez l'humainPMID 18801827
2. 2.Black et coll. 2011 : l'AVE1625 en association aux antipsychotiques, cognition et effets indésirables chez le rongeurPMID 21181124
3. 3.Herling et coll. 2007 : l'AVE1625 agit sur les paramètres métaboliques indépendamment de la prise alimentairePMID 17595216