Eact is a highly specific and potent activator of TMEM16A, which activates TMEM16A when the calcium ion concentration increases [1]. At no Ca²⁺ conditions, Eact significantly enhances the Cl- current, and increases the amplitude and frequency of isolated guinea pig ileum contraction [2]. Eact has been widely used to regulate the contraction of coronary artery smooth muscle and to control membrane potential[3].
In vivo, Eact treatment at a single dose (20μl; 4.67mM) via injecting into the paw of a mouse can induce a strong and persistent hyperalgesia to heat for 60 minutes[4]. Thirty minutes before the epilepsy test, a single dose of Eact (10mg/kg) was administered through the gastric intubation, which significantly reduced the severity of acoustically evoked seizures and decreased the frequency of wild running seizures (WRS) in rats[5].
References:
[1] Kunzelmann K, Ousingsawat J, Cabrita I, et al. TMEM16A in cystic fibrosis: activating or inhibiting?[J]. Frontiers in pharmacology, 2019, 10: 3.
[2] Hao A, Guo S, Shi S, et al. Emerging modulators of TMEM16A and their therapeutic potential[J]. The Journal of Membrane Biology, 2021, 254(4): 353-365.
[3] Dick G, Tune J. Smooth Muscle Contraction Is Regulated by Chloride Channels: Functional Evidence for TMEM16A in Porcine Coronary Arteries[J]. The FASEB Journal, 2021, 35.
[4] Liu S, Feng J, Luo J, et al. Eact, a small molecule activator of TMEM16A, activates TRPV1 and elicits pain‐and itch‐related behaviours[J]. British journal of pharmacology, 2016, 173(7): 1208-1218.
[5] Thomas M, Simms M, N’Gouemo P. Activation of calcium-activated chloride channels suppresses inherited seizure susceptibility in genetically epilepsy-prone rats[J]. Biomedicines, 2022, 10(2): 449.
Eact是一种高特异性、强效的TMEM16A激活剂，能在钙离子浓度升高时激活TMEM16A[1]。在无Ca2+条件下，Eact可显著增强Cl⁻电流，并增加离体豚鼠回肠收缩的幅度和频率[2]。Eact已被广泛用于调节冠状动脉平滑肌的收缩和膜电位控制[3]。
在体外，将单剂量（20µl；4.67mM）Eact注射到小鼠爪中，可诱导出持续60分钟的强效热痛觉过敏[4]。在癫痫试验前30分钟，通过灌胃单次给予10mg/kg剂量的Eact，可显著降低大鼠因声诱导的癫痫发作严重程度，并减少狂奔性癫痫发作的频率[5]。