Iptakalim hydrochloride

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].

Signaling Pathways >> Membrane Transporter/Ion Channel >> nAChR

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

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]. . Animal Model: Thirty male Sprague-Dawley rats weighing 275-299 grams[3]. Dosage: 0, 10, 30, or 60 mg/kg. Administration: IP, 10 min before the start of a 4-min test session. Result: Decreased chamber activity. Dipper entries following pretreatment with 30 and 60 mg/kg Iptakalim were significantly lower than with 0 (saline) or 10 mg/kg iptakalim pretreatment (Tukey HSD tests).

[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.