bkca a

BKCa activator-1 (Compound 51b) is an orally active activator of BKCa calcium-activated potassium channels with an EC50 of 2.82 μM. It promotes K+ efflux, leading to cell membrane hyperpolarization and inhibition of smooth muscle contraction. In a spontaneous hypertensive rat (SHR) model, it alleviates urinary incontinence and exhibits antitussive effects in a guinea pig cough model.

GAL-021 sulfate is a BKCa channel blocker that inhibits the analgesic effects of opioids and is used in the study of respiratory control diseases.

(±)-Naringenin (Naringenine) is a natural product. It displays vasorelaxant effect on endothelium-denuded vessels via the activation of BKCa channels in myocytes.

Flindokalner (BMS-204352) is a potassium channel modulator and a positive modulator of all neuronal Kv7 channel subtypes expressed in HEK293 cells. It is also a positive modulator of large conductance calcium-activated K channels (BKca) and displays negative modulatory activity at Kv7.1 channels (Ki = 3.7 μM). Additionally, Flindokalner acts as a negative modulator of GABAA receptors and demonstrates anxiolytic efficacy in vivo.

14S(15R)-EET is an oxylipin and a cytochrome P450 metabolite of arachidonic acid .114S(15R)-EET binds to isolated guinea pig monocytes with a Kivalue of 612.5 nM in a competitive binding assay using [3H]14(15)-EET.2It induces dilation of precontracted isolated canine epicardial arterioles (EC50= 4 pM) and denuded porcine subepicardial arterioles (EC50= 3 pM).3Unlike 14R(15S)-EET, 14S(15R)-EET does not inhibit COX in enzyme assays or isolated platelets.4 1.Daikh, B.E., Lasker, J.M., Raucy, J.L., et al.Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C91J. Pharmacol. Exp. Ther.271(3)1427-1433(1994) 2.Wong, P.Y.-K., Lai, P.-S., and Falck, J.R.Mechanism and signal transduction of 14 (R), 15 (S)-epoxyeicosatrienoic acid (14,15-EET) binding in guinea pig monocytesProstaglandins Other Lipid Mediat.62(4)321-333(2000) 3.Zhang, Y., Oltman, C.L., Lu, T., et al.EET homologs potently dilate coronary microvessels and activate BKCa channelsAm. J. Physiol. Heart Circ. Physiol.280(6)H2430-H2440(2001) 4.Fitzpatrick, F.A., Ennis, M.D., Baze, M.E., et al.Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acidsJ. Biol. Chem.261(2)15334-15338(1986)

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .1,217R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BKCa) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.2It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC50= ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.3,4 1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)

BMS-191011 (BMS-A) is an activator of large-conductance calcium-activated potassium (BKCa) channels ,effective in stroke models