Pinacidil monohydrate is an antihypertensive drug belonging to the class of potassium channel openers. Pinacidil monohydrate relaxes vascular smooth muscle by activating ATP-sensitive potassium channels[1-2]. Pinacidil monohydrate exhibits neuroprotective effects and improves blood lipid metabolism[3-4].
In vitro, treatment of HEK293T cells expressing SUR2B/Kir6.1 or SUR2B/Kir6.2 potassium channel complexes with Pinacidil monohydrate (100–300µM) for 24 hours, Pinacidil monohydrate significantly enhanced the activation of SUR2B/Kir6.1 channels by nucleotide di- or triphosphates (e.g., ATP, ADP, GTP, UDP). Pinacidil monohydrate was achieved by increasing the efficacy of nucleotides on slow gating mechanisms, thereby augmenting the number of functional channels[5]. Treatment of HepG2 human hepatoma cells with Pinacidil monohydrate (1mM) for 48 hours induced an increase in intracellular K⁺ and Na⁺ concentrations via activation of the Na⁺, K⁺, Cl⁻ cotransporter (NKCC). Pinacidil monohydrate led to a sustained rise in intracellular Ca²⁺ concentration through reverse activation of the Na⁺/Ca²⁺ exchanger, ultimately resulting in apoptosis[6].
In vivo, pretreatment of rats via intraperitoneal injection with Pinacidil monohydrate (10–50μg/kg) before skin/muscle incision and retraction (SMIR) surgery, Pinacidil monohydrate significantly inhibited the decrease in microvessel density (MVD) and glucose transporter-1 (GLUT1) expression in the peri-incisional microenvironment[7]. Pretreatment of C57BL/6J mice via intraperitoneal injection with Pinacidil monohydrate (0.1–0.5mg/kg/day) for three days prior to myocardial ischemia-reperfusion (I/R) injury, Pinacidil monohydrate significantly improved cardiac function, increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduced serum BNP levels[8].
References:
[1] Ahnfelt-Rønne I. Pinacidil. Preclinical investigations. Drugs. 1988;36 Suppl 7:4-9.
[2] Friedel HA, Brogden RN. Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. Drugs. 1990 Jun;39(6):929-67.
[3] Pereira AT, Gelfuso ÉA, Beleboni RO. Repositioning pinacidil and its anticonvulsant and anxiolytic properties in murine models. Sci Rep. 2024 Sep 30;14(1):22695.
[4] Shukry M, Kamal T, Ali R, et al. Pinacidil and levamisole prevent glutamate-induced death of hippocampal neuronal cells through reducing ROS production. Neurol Res. 2015 Oct;37(10):916-23.
[5] Satoh E, Yamada M, Kondo C, et al. Intracellular nucleotide-mediated gating of SUR/Kir6.0 complex potassium channels expressed in a mammalian cell line and its modification by pinacidil. J Physiol. 1998 Sep 15;511 ( Pt 3)(Pt 3):663-74.
[6] Kim JA, Kang YY, Lee YS. Activation of Na(+), K(+), Cl(-)-cotransport mediates intracellular Ca(2+) increase and apoptosis induced by Pinacidil in HepG2 human hepatoblastoma cells. Biochem Biophys Res Commun. 2001 Feb 23;281(2):511-9.
[7] Cao S, Qin Y, Chen J, et al. Effects of pinacidil on changes to the microenvironment around the incision site, of a skin/muscle incision and retraction, in a rat model of postoperative pain. Mol Med Rep. 2015 Jul;12(1):829-36.
[8] Liu M, Li S, Yin M, et al. Pinacidil ameliorates cardiac microvascular ischemia-reperfusion injury by inhibiting chaperone-mediated autophagy of calreticulin. Basic Res Cardiol. 2024 Feb;119(1):113-131.
Pinacidil monohydrate一种抗高血压药物，属于钾通道开放剂，通过激活ATP敏感性钾通道使血管平滑肌松弛[1-2]。Pinacidil monohydrate具有保护神经系统，及改善血脂代谢作用[3-4]。
在体外，Pinacidil monohydrate（100–300µM）处理表达SUR2B/Kir6.1或SUR2B/Kir6.2复合钾通道的HEK293T细胞24h，显著增强核苷酸二磷酸或三磷酸（如ATP、ADP、GTP、UDP）对SUR2B/Kir6.1通道的激活作用，并通过提高核苷酸对慢门控机制的效能增加功能通道数量[5]。Pinacidil monohydrate（1mM）处理HepG2人肝癌细胞48小时，通过激活Na⁺，K⁺，Cl⁻共转运体（NKCC）诱导细胞内K⁺浓度和Na⁺浓度升高，通过反向激活Na⁺/Ca²⁺交换体引起细胞内Ca²⁺浓度持续增加，最终导致细胞凋亡[6]。
在体内，Pinacidil monohydrate（10–50μg/kg）于皮肤/肌肉切开牵拉术（SMIR）前腹腔注射预处理大鼠，显著抑制术后切口周围微环境中的微血管密度（MVD）下降和葡萄糖转运蛋白-1（GLUT1）表达减少[7]。Pinacidil monohydrate（0.1–0.5mg/kg/day）于心肌缺血再灌注（I/R）损伤前3天腹腔注射预处理C57BL/6J小鼠，显著改善心脏功能，提高左室射血分数（LVEF）和左室短轴缩短率（LVFS），并降低血清BNP水平[8]。