Rimonabant belongs to the new drug class of cannabinoid-1 receptor antagonists and is able to decrease appetite and food intake and thus stimulates weight loss. Rimonabant is indicated for severe obesity and obese patients with diabetes type 2 or hyperlipidemia as an adjunct of lifestyle changes.

The endocannabinoïd system controls regulation of food intake and appetite in the brain and lipogenesis in the adipose tissue (see graphic below). The receptors of this system are located in the brain and in peripheral tissues, such as adipose tissue. The endogenous agonist in the brain is called anandamide. It is already known, that the effective substance from cannabis delta-tetrahydrocannabinol (THC) increases appetite. So, an antagonist should be able to decrease appetite. In obese patients, the endocannabinoïd system is disregulated.

Mechanism: a presynaptic stimulus leads to release of neurotransmitters GABA and glutamate. These neurotransmitters bind to a postsynaptic receptor which results

in a postsynaptic response. Endocannabinoids (natural ligand anandamide) or THC bind to the endocannabinoid receptor (CB1) and decrease the release of GABA and glutamate (not shown in this graphic). Rimonabant blocks the CB1-receptor and thus increases the release of neurotransmitters GABA and glutamate.

Safety concerns limit the clinical applicability of the drug. Because of the neurological and psychiatric adverse effects of rimonabant, the drug has not been approved in the US. In Europe, rimonabant has been approved, but major depression and the use of anti-depressants is a contraindication for its use. Other adverse effects include nausea, diarrhea and vomiting.

Rimonabant is no longer authorised in the EU.

EPAR of rimonabant. This drug has been withdrawn from the authorised drug list.