EMPA

EMPA is a high-affinity, reversible and selective orexin OX₂ receptor antagonist. [³H]EMPA binds to human and rat OX₂-HEK293 membranes with K_D values of 1.1 and 1.4 nM respectively^[1]. In Vitro: 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 K_i values of 1.10±0.24 nM and 1.45±0.13 nM, respectively^[1].
EMPA shows an IC₅₀=5.75 µM, K_i=2.63 µM, and IC₅₀=12.8 µM, K_i=5.8 µM in the binding assay at human and mouse V_1a 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]. In Vivo: 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].