6533b82afe1ef96bd128c305

RESEARCH PRODUCT

The role of (E)-6-chloro-3-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-2-styrylquinazolin-4(3H)-one in the modulation of cannabinoidergic system. A pilot study

Benedetta MaggioAnna EbrancatoFulvio PlesciaGiuseppe DaidoneDemetrio RaffaFabiana PlesciaAngela CavallaroMaria Valeria RaimondiCarla CannizzaroGianluca Lavanco

subject

0301 basic medicineAgonistCannabinoid receptormedicine.drug_classmedicine.medical_treatmentPilot ProjectsPharmacologyCannabinoidergicStyrenes03 medical and health sciences0302 clinical medicineRimonabantmedicineAnimalsRats WistarLatency (engineering)PharmacologyDose-Response Relationship DrugCannabinoid CB1 receptor antagonist Quinazolinone derivate Tetrad task Declarative memoryCannabinoidsChemistryRecognition PsychologyGeneral MedicineCyclohexanolsEndocannabinoid systemSettore CHIM/08 - Chimica FarmaceuticaRats030104 developmental biologyNociceptionQuinazolinesSettore BIO/14 - FarmacologiaCannabinoidLocomotion030217 neurology & neurosurgerymedicine.drug

description

Abstract Background Compounds acting on endocannabinoid system regulate different neuronal processes through the cannabinoid receptors activation. The main aim of this study was determining whether the 2-styrylquinazolin-4(3H)-one 5, a structural analogue of rimonabant, was able to counteract the behavioural signs of the activation of the endocannabinoidergic system induced by CP 55.940. Methods Behavioural assessment was carried out using the tetrad task and the novel object recognition test. The endocannabinoidergic system activation was possible by the administration of CP 55.940 and 30 min after rats were tested in the tetrad task for the evaluation of the antinociceptive-, cataleptic-, hypothermic- and locomotor- effects. The evaluation of the declarative memory was carried out through the novel object recognition test. The administration of the new compound was made at three different doses, 30 min before CP 55.940 administration on a separate group of animals. Results Our results demonstrated that compound 5, at the highest dose, was able to counteract the effects exerted by CP 55.940, shown by an increase in body temperature, total distance travelled, latency to fall and decrease in tail flick latency, interfering conjointly in memory impairment. Conclusion This study shows that compound 5 is able to counteract the cannabinoid activation induced by the agonist CP 55.940. Further investigations on its pharmacological profile are mandatory before considering it as a potential candidate for clinical studies and its possible employment as pharmacological agent for the management of different pathological conditions such as motor incoordination, obesity and brain related disorders.

10.1016/j.pharep.2018.06.004http://hdl.handle.net/10447/302745