Pinacidil is a strong potassium channel opener and antihypertensive agent that hyperpolarizes vascular smooth muscle by activating K+-channels. It significantly enhances reperfusion function and cardiac compliance and exhibits direct cardioprotective effects[1].
Pinacidil/吡那地尔 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Kir6.1/SUR2B HEK-293 stable cell line
100 µM
10 minutes
To test the effect of Pinacidil on Kir6.1/SUR2B channel activation, results showed that Pinacidil effectively activated the channel.
Front Pharmacol. 2023 Jun 20;14:1197257
Kir6.2/SUR2A HEK-293 stable cell line
9 µM
10 minutes
To test the effect of Pinacidil on Kir6.2/SUR2A channel activation, results showed that Pinacidil effectively activated the channel with an EC50 of 11 µM.
Front Pharmacol. 2023 Jun 20;14:1197257
Human cardiac microvascular endothelial cells (HCMECs)
0.1 or 10 µM
12 hours hypoxia followed by reoxygenation
Pinacidil treatment improved cell viability and proliferation, reduced the ratio of TUNEL-positive cells, downregulated mitochondria-related apoptosis proteins Bax, Caspase 9, and cleaved-Caspase 3, and reduced cytochrome C (Cyt-C) release. Additionally, pinacidil increased NO content and eNOS expression and phosphorylation at Ser1177, reduced ICAM-1 and VCAM-1 expression, and improved endothelial barrier function.
Basic Res Cardiol. 2024 Feb;119(1):113-131
Guinea-pig isolated perfused heart
10, 30, 50 µM
15 min
To study the effects of pinacidil on cardiac contractility, coronary perfusion pressure, and ECG intervals. Results showed that pinacidil decreased +dP/dtmax, cP, and QT interval in a dose-dependent manner, increased PR interval, and did not modify QRS duration.
Br J Pharmacol. 1992 Mar;105(3):715-9
Retinal microglia
10, 50, 100 µM/3 µL
16 hours
Pinacidil inhibited tumor necrosis factor and interleukin-1β expression in M1-type microglia and alleviated the M1 microglia-induced GFAP expression in the Müller cells. Furthermore, pinacidil on its own, or in combination with IL-4, can upregulate arginase-1 (Arg-1) and Kir6.1 expression in microglial cells.
Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):3
Human immortalized renal proximal tubule cells (RPTECs/TERT1)
100 µM
21 days
To evaluate the role of KATP channels in tubulogenesis, results showed chronic activation of KATP channels led to denser tubular structures but shorter tubule length
ACS Biomater Sci Eng. 2022 Mar 14;8(3):1239-1246
Guinea-pig taenia caecum smooth muscle
0.1-100 µM
30 minutes
Both pinacidil and GTN inhibited spontaneous tone, and these inhibitory effects were not antagonized by apamin.
Br J Pharmacol. 1987 Jun;91(2):421-9
Rat portal vein smooth muscle
0.3-30 µM
30 minutes
Pinacidil completely abolished spontaneous electrical and mechanical activity and inhibited contractions induced by noradrenaline and 20 mM K+, but had no significant effect on responses to 80 mM K+.
Br J Pharmacol. 1987 Jun;91(2):421-9
Rat aortic smooth muscle
1-100 µM
30 minutes
Pinacidil inhibited contractions induced by noradrenaline and KCl, showing selective inhibition of contractions to 20 mM K+ but little effect on responses to 80 mM K+.
Br J Pharmacol. 1987 Jun;91(2):421-9
Rat mesenteric resistance vessel smooth muscle cells
0.3-10 µM
5 minutes
To study the inhibitory effect of Pinacidil on noradrenaline-induced tone, results showed Pinacidil concentration-dependently suppressed the tone.
Br J Pharmacol. 1988 Sep;95(1):103-8
Astrocytes
400 µM
50 seconds
To evaluate Pinacidil's effect on astrocytic membrane potential, revealing only slight depolarization by ethanol (1.3 ± 1.7 mV) and no significant impact of Pinacidil
Cleve Clin J Med. 2009 Apr;76 Suppl 2(0 2):S80-5
Neurons
400 µM
50 seconds
To assess the impact of Pinacidil on neuronal biophysical properties, showing no significant changes in resting membrane potential, input resistance, or current-induced spike rate
Cleve Clin J Med. 2009 Apr;76 Suppl 2(0 2):S80-5
Rat mesenteric resistance vessel smooth muscle cells
1-10 µM
6 minutes
To study the effect of Pinacidil on potassium channels, results showed Pinacidil significantly increased the 42K-efflux rate constant.
Br J Pharmacol. 1988 Sep;95(1):103-8
Rat cerebral cortex cells
1 mM
60 minutes
MgATP enhanced the inhibitory effect of pinacidil on [3H]-glibenclamide binding.
Br J Pharmacol. 1992 Jun;106(2):295-301
HIT-T15 cells
200-500 µM
60 minutes
In the absence of MgATP, pinacidil did not significantly displace [3H]-glibenclamide binding; however, in the presence of MgATP, pinacidil significantly enhanced the displacement of [3H]-glibenclamide binding.
Br J Pharmacol. 1992 Jun;106(2):295-301
Guinea-pig tracheal smooth muscle
0.1-100 µM
8 minutes
Pinacidil fully relaxed spontaneous tone and selectively inhibited contractions to 20 mM K+, but had no significant effect on responses to 80 mM K+.
Br J Pharmacol. 1987 Jun;91(2):421-9
Rabbit portal vein smooth muscle cells
>3 µM
several minutes
Pinacidil inhibited the ryanodine-sensitive oscillatory outward potassium current induced by Ca released from an intracellular store, and glibenclamide antagonized this effect.
Br J Pharmacol. 1991 Apr;102(4):788-90
Pinacidil/吡那地尔 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
SUR2[R1154Q] mutant mice
Intraperitoneal injection
0.01, 0.1, 1 mg
Daily
To evaluate the effect of Pinacidil on blood pressure and heart rate, results showed significantly weakened blood pressure-lowering effect in SUR2RQ/RQ mice, but similar heart rate-increasing effect
JCI Insight. 2021 Mar 8;6(5):e145934
C57BL/6J mice
Cardiac microvascular ischemia-reperfusion (I/R) injury model
Intraperitoneal injection
0.1 or 0.5 mg/kg/day
Once daily for 3 days
Pinacidil treatment improved cardiac function (LVEF and LVFS), reduced infarction size and myocardial fibrosis, decreased endothelial apoptosis, increased capillary density and perfusion, and reduced the no-reflow phenomenon. Additionally, pinacidil increased NO generation, reduced ET-1 expression, improved endothelial barrier function, and reduced vascular leakage and inflammation.
Basic Res Cardiol. 2024 Feb;119(1):113-131
Guinea-pigs and rabbits
Mesenteric arteries
Superfusion
1 μM to 30 μM
Not specified
Pinacidil inhibited neuromuscular transmission in guinea-pig and rabbit mesenteric arteries, reducing the amplitude and decay time of excitatory junction potentials (ej.ps), with minimal effects on NA and DOPEG overflow. This inhibition was prevented by glibenclamide.
Br J Pharmacol. 1990 Nov;101(3):581-6
Sprague Dawley rats
Skin/muscle incision and retraction (SMIR) surgery model
Intraperitoneal injection
10 µg/kg, 25 µg/kg, 50 µg/kg
Single dose before surgery
To evaluate the effects of Pinacidil on SMIR surgery-induced mechanical allodynia. Results showed that Pinacidil significantly inhibited SMIR-induced mechanical allodynia and improved the microenvironment around the incision site.
Mol Med Rep. 2015 Jul;12(1):829-36
Wistar rats
Middle cerebral artery occlusion (MCAO) model
Intracerebroventricular injection
10 nmol/5 μL
Single dose, 30 min before cerebral ischemia
To investigate the effect of Pinacidil on neuronal apoptosis and its signaling transduction mechanism following cerebral ischemia-reperfusion. Results showed that Pinacidil significantly reduced neuronal apoptosis and decreased the expressions of caspase-3, caspase-8, and caspase-9 mRNAs.
Neurosci Bull. 2007 May;23(3):145-50
Sprague-Dawley rats
Isolated myocardial ischemia-reperfusion model
Perfusion
10, 30, 50 µM
Single administration, lasting 2 minutes
To investigate the protective effects and mechanisms of different concentrations of Pinacidil postconditioning on myocardial ischemia-reperfusion injury in rats. Results showed that 50 μmol/l Pinacidil postconditioning activated the Nrf2-ARE pathway, reduced ROS generation, significantly improved cardiac function, and alleviated myocardial injury.
Mol Med Rep. 2021 Jun;23(6):433
Guinea-pigs
Langendorff perfused heart model
Perfusion
10, 30, 50 μM
15 min
To study the effects of pinacidil on cardiac rhythm. Results showed sustained ventricular fibrillation (VF) in 4 out of 20 hearts, and the induction of VF was concentration-dependent.
Br J Pharmacol. 1992 Mar;105(3):715-9
Sprague Dawley (SD) rats
Streptozotocin-induced diabetic rats
Intravitreal injection
10, 50, or 100 μM
Single injection, samples harvested at 24 hours
Intravitreal injection of pinacidil alleviated diabetes-induced Müller cell gliosis and microglial activation and reduced vascular endothelial growth factor expression.
Invest Ophthalmol Vis Sci. 2021 Feb 1;62(2):3
Human hearts
Congestive heart failure (CHF) and non-failing (NF) hearts
Coronary perfusion
100 μM
10 minutes
Pinacidil significantly decreased APDs in both atria and ventricles in all hearts studied and induced atrial and ventricular flutter/fibrillation.
J Mol Cell Cardiol. 2011 Aug;51(2):215-25
Rats
PTZ and pilocarpine-induced seizure models
Intraperitoneal injection
2.5, 5, 10 mg/kg
Single administration, observed for 30 minutes (PTZ) or 45 minutes (pilocarpine)
To evaluate the anticonvulsant and anxiolytic effects of Pinacidil. Results showed that 10 mg/kg dose fully protected animals from PTZ-induced seizures, and 2.5, 5, and 10 mg/kg doses provided 85.7%, 100%, and 100% protection against pilocarpine-induced seizures, respectively. Additionally, Pinacidil demonstrated mild anxiolytic activity.
Sci Rep. 2024 Sep 30;14(1):22695
C57BL/6 mice
Anesthetized rats and awake mice
Topical cortical application
220 or 440 μM
Single administration, effects lasting ~50-60 seconds
To assess Pinacidil's effect on vascular diameter and local blood volume, showing MCA dilation (~20% peak) and parenchymal blood volume increase (~2% peak), mimicking functional hyperemia
Cleve Clin J Med. 2009 Apr;76 Suppl 2(0 2):S80-5
Sprague-Dawley rats
Anesthetized rats and awake mice
Topical cortical application
400 μM
Single administration, effects lasting ~50-60 seconds
To assess Pinacidil's effect on vascular diameter and local blood volume, showing MCA dilation (~20% peak) and parenchymal blood volume increase (~2% peak), mimicking functional hyperemia
Cleve Clin J Med. 2009 Apr;76 Suppl 2(0 2):S80-5
Mice
Hypokalaemic periodic paralysis model
Ex vivo bath application
8.1±0.5 μM
Single dose
Test the protective effect of Pinacidil on muscle force loss under low-K+ conditions, showing it was about 10-fold less potent than Retigabine
Brain. 2023 Apr 19;146(4):1554-1560
Beagles
Ventricular fibrillation model
Intravenous
Loading dosage 0.5 mg/kg and maintenance dosage 0.5 mg/kg/h
Loading dose given in 10 min, maintenance dosage continued until the end of the experiment
Pinacidil significantly decreased APD 90 and ARI, increased VF activation rate, but did not change DFT. The drug significantly prolonged the postshock cycle length of cycles 2 to 5 for the successful episodes suggesting that EAD may play a role in postshock activation.
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