EMPA

EMPA is a selective, high-affinity and reversible antagonist of orexin OX2 receptor (human and rat OX2-HEK293 membranes with KD values of 1.1 and 1.4 nM respectively) EMPA displaces the 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. 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. 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.EMPA competitively antagonizes orexin-A-and orexin-B-evoked accumulation of inositol phosphates (IP) at hOX2 receptors with pA2 values of 8.6 and 8.8 respectively. 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.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.