Iptakalim hydrochloride
目录号 : GC63928
Iptakalim hydrochloride 是亲脂性的对氨基化合物，是 ATP 敏感的钾通道 (KATP) 的开放剂，也是包含α4β2 的烟碱乙酰胆碱受体 (nAChR)拮抗剂。
Cas No.:642407-63-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Iptakalim hydrochloride, a lipophilic para-amino compound, is a novel ATP-sensitive potassium channel (KATP) opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist[1].
Iptakalim (Ipt) hydrochloride has been shown to reverse pulmonary resistance vascular remodeling, inhibit proliferation of pulmonary arterial smooth muscle cells (PASMCs) and airway smooth muscle cells (ASMCs), as well as protect PAECs from pathological stimulation[1].Iptakalim has an inhibitory effect on [Ca2+]cyt increase and the proliferation of pulmonary arterial SMCs induced by endothelin-1 through activation of KATP channels. Iptakalim (10 μM, 10 min) pretreatment of pulmonary arterial SMCs significantly prevents ransient ncrease of [Ca2+]cyt elicited by endothelin-1[2].Iptakalim at he concentrations of 0.1, 1, and 10 AM lowered[3H]thymidine incorporation by 19.75±4.60% (n=10), 41.20±9.49% (n=10), and 54.74±10.11% (n=10), respectively, compared with that of cells treated only with endothelin-1[2].
Iptakalim (10-60 mg/kg) attenuates nicotine-evoked conditioned responding. Iptakalim also attenuates chamber activity in these nicotine test sessions[3]..Iptakalim (60 mg/kg) pretreatment significantly reduced activity (LSD comparisons)[3]..
[1]. Mengyu He, et al. Iptakalim ameliorates hypoxia-impaired human endothelial colony-forming cells proliferation, migration, and angiogenesis via Akt/eNOS pathways. Pulm Circ. 2019 Oct 18;9(3):2045894019875417.
[2]. Weiping Xie, et al. Anti-proliferating effect of iptakalim, a novel KATP channel opener, in cultured rabbit pulmonary arterial smooth muscle cells. Eur J Pharmacol. 2005 Mar 28;511(2-3):81-7.
[3]. S Charntikov, et al. Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine. Neuropharmacology. 2013 Dec;75:138-44.
| Cas No. | 642407-63-4 | SDF | Download SDF |
| 分子式 | C9H22ClN | 分子量 | 179.73 |
| 溶解度 | Water : 25 mg/mL (139.10 mM; ultrasonic and warming and heat to 70°C) | 储存条件 | 4°C, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.5639 mL | 27.8195 mL | 55.639 mL |
| 5 mM | 1.1128 mL | 5.5639 mL | 11.1278 mL |
| 10 mM | 0.5564 mL | 2.782 mL | 5.5639 mL |
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Effects of Iptakalim hydrochloride, a novel KATP channel opener, on pulmonary vascular remodeling in hypoxic rats
Life Sci 2004 Sep 10;75(17):2065-76.PMID:15312751DOI:10.1016/j.lfs.2004.03.031.
To investigate whether pulmonary artery remodeling could be prevented or not in hypoxic pulmonary hypertensive rats by treatment, the effects of Iptakalim hydrochloride, a novel KATPCO, were evaluated. Iptakalim hydrochloride was orally administered at the doses of either 1.5 mg/kg/day or 0.75 mg/kg/day before their 4-week exposure to hypoxia (10% oxygen). It was demonstrated that Iptakalim hydrochloride could reverse all pathological indices of pulmonary arterial remodeling and significantly reduce right ventricular hypertrophy in hypoxic rats. The reversal of hypoxic indices was dose-dependent, in which the higher dose of Iptakalim hydrochloride reversed pathological indices more effectively than the lower dose did. This was further confirmed electrophysiologically using whole cell patch-clamp technique, which revealed that the outward potassium currents could be enhanced by Iptakalim hydrochloride, and the decrease of K+ current density and increase of membrane capacitance could be reversed by chronic Iptakalim hydrochloride treatment. These findings implied that Iptakalim hydrochloride could play its role through activating plasmalemmal K+ channels of pulmonary arterial SMCs. The results indicated that Iptakalim hydrochloride had anti-remodeling properties of pulmonary artery in hypoxic pulmonary hypertensive rats. It is therefore suggested that KATPCOs might be promising in the treatment of patients with hypoxic, and even possibly other forms of, pulmonary hypertension.
Single-dose pharmacokinetics and safety of Iptakalim hydrochloride in Chinese healthy volunteers
J Pharm Pharmacol 2012 Mar;64(3):337-43.PMID:22309265DOI:10.1111/j.2042-7158.2011.01411.x.
Objectives: To investigate the safety, pharmacokinetics and food effect of iptakalim in healthy adult Han Chinese volunteers. Methods: Study 1 was a randomized open-label, Latin square designed, single-dose, three-period, self-control crossover study. Six men and six women received 5, 10 and 20 mg of iptakalim orally. Study 2 was a randomized, open-label, single-dose, two-period, self-control crossover study. Ten men were included and each subject received 5 mg iptakalim orally, fasting and nonfasting. Key findings: No adverse effects were reported and no clinically meaningful changes in vital signs were found. Cmax, AUC(0-t) and AUC(0-∞) were proportional over the dose levels of 5, 10 and 20 mg. Tmax, t½ and CL/F were similarly independent of dose level. In the 5 mg and 20 mg group, the Cmax, AUC(0-t) and AUC(0-∞) in women were significantly higher than in men, although they showed no difference after correction by mg/kg doses in the 5 mg group. At the 5-mg dose level, no significant difference in pharmacokinetics was found in nonfasting and fasting subjects. Conclusions: Single-dose pharmacokinetics of iptakalim showed dose proportionality over the dose levels of 5-20 mg. The pharmacokinetics showed gender differences in the 5 and 20 mg groups. Food had almost no impact on the pharmacokinetics at the 5 mg level.
Evaluation of the Potential Effect of Iptakalim hydrochloride on the QT Interval in Single- and Multiple-Ascending-Dose Studies Using Concentration-QTc Analysis
Clin Pharmacol Drug Dev 2021 Oct;10(10):1231-1241.PMID:33855805DOI:10.1002/cpdd.945.
Cardiotoxicity has been one of the most common causes of withdrawal of drugs from the market, and prolongation of the QT interval is one of the manifestations of drug cardiotoxicity. Iptakalim hydrochloride (ITKL) is a selective ATP-sensitive potassium channel opener used to treat hypertension. It is crucial to assess the risk of cardiac repolarization of ITKL in clinical trials. This study was conducted to determine the effect of ITKL on corrected QT (QTc) interval. A randomized, double-blind, placebo-controlled single- and multidose regimen was carried out to investigate the QTc and ITKL concentration correlation. ITKL was administered at doses of 5, 10, 15, and 20 mg with single oral administration and 10 and 20 mg with multiple oral administration, along with placebo, in 83 healthy subjects. Electrocardiograms (ECGs) and blood samples were collected on a preset time schedule. A ΔΔQTcF effect above 10 milliseconds was excluded at all observed plasma levels. Among them, the highest dose was 20 mg, which is twice the therapeutic dose. We concluded that ITKL did not prolong the QT interval in healthy subjects within the therapeutic dose. Retrospectively registered: The study was registered at Chinese Clinical Trial Registry with registration number ChiCTR1800014466.
Iptakalim hydrochloride protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models
Brain Res 2005 Jul 5;1049(1):80-8.PMID:15932749DOI:10.1016/j.brainres.2005.04.073.
Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits K(ATP) channel activation. Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. Chronic exposure of cultured PC12 cells to neurotoxins, such as 6-OHDA, MPP+, or rotenone, decreased overall [3H]-glutamate uptake in a concentration-dependent manner. Pre-treatment using 10 microM Ipt significantly protected cells against neurotoxin-induced glutamate uptake diminishment, and this protection was abolished by the K(ATP) channel blocker glibenclamide (20 microM), suggesting that the protective mechanisms may involve the opening of K(ATP) channels. In 6-OHDA-treated rats (as an in vivo Parkinson's disease model), [3H]-glutamate uptake was significantly lower in synaptosomes isolated from the striatum and cerebral cortex, but not the hippocampus. Pre-conditioning using 10, 50, and 100 microM Ipt significantly restored glutamate uptake impairment and these protections were abolished by blockade of K(ATP) channels. It is concluded that Ipt exhibits substantial protection of cells against neurotoxicity in in vitro and in vivo models. The cellular mechanisms of this protective effect may involve the opening of K(ATP) channels. Collectively, Ipt may serve as a novel and effective drug for PD therapy.
Iptakalim inhibits nicotinic acetylcholine receptor-mediated currents in dopamine neurons acutely dissociated from rat substantia nigra pars compacta
Neurosci Lett 2006 Jul 31;403(1-2):57-62.PMID:16730119DOI:10.1016/j.neulet.2006.04.060.
Iptakalim hydrochloride, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, has shown remarkable antihypertensive and neuroprotective effects in a variety of studies using in vivo and in vitro preparations. We recently found that iptakalim blocked human alpha4-containing nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the human SH-EP1 cell line. In the present study, we examined the effects of iptakalim on several neurotransmitter-induced current responses in single DA neurons freshly dissociated from rat substantia nigra pars compacta (SNc), using perforated patch-clamp recordings combined with a U-tube rapid drug application. In identified DA neurons under voltage-clamp configuration, glutamate-, NMDA-, and GABA-induced currents were insensitive to co-application with iptakalim (100 microM), while whole-cell currents induced by ACh (1 mM+1 microM atropine) or an alpha4beta2 nicotinic acetylcholine receptors relatively selective agonist, RJR-2403 (300 microM), were eliminated by iptakalim. Iptakalim inhibited RJR-2403-induced current in a concentration-dependent manner, and reduced maximal RJR-2403-induced currents at the highest agonist concentration, suggesting a non-competitive block. In current-clamp mode, iptakalim failed to affect resting membrane potential and spontaneous action potential firing, but abolished RJR-2403-induced neuronal firing acceleration. Together, these results indicate that in dissociated SNc DA neurons, alpha4-containing nAChRs, rather than ionotropic glutamate receptors, GABA(A) receptors or perhaps K-ATP channels are the sensitive targets to mediate iptakalim's pharmacological roles.