Endocannabinoid receptors type 1 and 2 can be managed by pharmacological compounds to regulate different neuronal processes. Hyperactivity or dysfunction in the endocannabinoid system might be implicated in disturbance or abnormality of neural processes, evidencing its relevance for several pathologies. The reported study shows that a new structural analogue of rimonabant, (E)-6-chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2-styrylquinazolin-4(3H)-one (1), is able to counteract the behavioral signs of the activation of the endocannabinoidergic system induced by the administration of the agonist CP 55,940.

The analogue of rimonabant (1) is characterized by a quinazolinone structure bearing a heterocyclic pyrazole nucleus. Behavioral assessment was carried out by tetrad task and the novel object recognition tested on rats, to evaluate cannabinoid effects on declarative memory. The endocannabinidergic system was activated by the administration of the cannabinoid agonist CP 55,940.

Our study shows that compound 1 at the dose of 10 mg/kg, 30 min before CP 55,940 administration, is able to counteract the effects exerted by CP 55,940, as shown by an increase in body temperature, in total distance travelled, in latency to fall down and a decrease in tail flick latency. Furthermore, the memory impairment induced by the cannabinoid agonist is prevented by compound 1 showing that it is able to counteract the cannabinoid activation induced by the agonist CP 55,940. Further investigations are in progress to evaluate the pharmacological profile of compound 1 and consider it as a potential candidate for clinical studies and as pharmacological agent in managing different pathological conditions as motor incoordination, obesity, and brain related disorders