EMPA

EMPA is a high-affinity, reversible and selective orexin OX2 receptor antagonist. [3H]EMPA binds to human and rat OX2-HEK293 membranes with KD values of 1.1 and 1.4 nM respectively[1].

Signaling Pathways >> GPCR/G Protein >> Orexin Receptor (OX Receptor)

Research Areas >> Neurological Disease

OX2 Receptor

EMPA competitively antagonizes orexin-A-and orexin-B-evoked accumulation of [3H]inositol phosphates (IP) at hOX2 receptors with pA2 values of 8.6 and 8.8 respectively[1]. EMPA displaces the [3H]EMPA binding from cell membranes containing human and rat OX2 receptors, with Ki values of 1.10±0.24 nM and 1.45±0.13 nM, respectively[1]. EMPA shows an IC50=5.75 µM, Ki=2.63 µM, and IC50=12.8 µM, Ki=5.8 µM in the binding assay at human and mouse V1a receptors, respectively[1]. In CHO(dHFr-) cells stably expressing hOX2 receptors, EMPA inhibits orexin-A-or orexin-B-evoked [Ca2+]i response with IC50s of 8.8±1.7 nM and 7.9±1.7 nM, respectively[1].

EMPA (1-300 mg/kg; i.p.) dose-dependently reverses this [Ala11,D-Leu15]orexin-B-induced hyperlocomotion without itself significantly affecting locomotor activity (LMA) in male NMRI mice[1]. EMPA (3-30 mg/kg; i.p.) induces a significant and dose-dependent reduction in the baseline LMA in france and male Wistar rats. EMPA (3-30 mg/kg; i.p.) demonstrates a clear dose-dependent inhibition of spontaneous activity as compared with vehicle-treated animals[1]. Animal Model: Male NMRI mice (20-30 g)[1] Dosage: 1, 3, 10, 30, 100, 300 mg/kg Administration: Injected i.p. at a volume of 10 mL/kg Result: Dose-dependently reversed this [Ala11,D-Leu15]orexin-B-induced hyperlocomotion without itself significantly affecting LMA. Animal Model: France and Male Wistar rats (196-237 g)[1] Dosage: 3, 10, 30 mg/kg Administration: Injected i.p. at a volume of 5 mL/kg Result: Induced a significant and dose-dependent reduction in the baseline LMA. Demonstrated a clear dose-dependent inhibition of spontaneous activity as compared with vehicle-treated animals.

[1]. P Malherbe, et al. Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX₂ receptor. Br J Pharmacol. 2009 Apr; 156(8): 1326-1341.