Novel electropharmacological activity of amiodarone on human HCN channels heterologously expressed in the Xenopus oocytes

Fan, Xiaoliang; Chen, Yongjun; Wu, Pan; Xing, Junlian; Chen, Hui; Song, Tao; Yang, Jing; Zhang, Jun; Huang, Congxin

doi:10.1016/j.ejphar.2011.07.039

Cited by 8 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 ) has been tested also on human HCN1, 2 and 4 isoforms expressed in Xenopus oocytes [169]. The compound blocked the current mediated by the three isoforms with some preference for HCN4 (IC 50 2.1±1.9 μM) with respect to HCN2 (IC 50 8.2±4.2 μM) and HCN1 (IC 50 46.3±11.7μM), without modifying the voltage dependence of activation.…”

Section: Substances That Have Been Shown To Modulate Hcn Channel Actimentioning

confidence: 99%

“…Indeed, for some of them the interaction site is suggested to be located on the extracellular side (niflumic acid [180], loperamide [147], tramadol [151], clonidine [17]), in the intracellular region of the pore (ZD7288 [186], cilobradine and ivabradine [186, 216], nicotine [183], lidocaine [165], amiodarone [169]) or within the cyclic nucleotide binding domain (eugenol [192], fisetin [199])…”

Section: The Location Of the Interaction Site(s)mentioning

confidence: 99%

See 1 more Smart Citation

HCN Channels Modulators: The Need for Selectivity

Romanelli

Sartiani²,

Masi³

et al. 2016

CTMC

View full text Add to dashboard Cite

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, the molecular correlate of the hyperpolarization-activated current (I f /I h ), are membrane proteins which play an important role in several physiological processes and various pathological conditions. In the Sino Atrial Node (SAN) HCN4 is the target of ivabradine, a bradycardic agent that is, at the moment, the only drug which specifically blocks I f . Nevertheless, several other pharmacological agents have been shown to modulate HCN channels, a property that may contribute to their therapeutic activity and/or to their side effects.HCN channels are considered potential targets for developing drugs to treat several important pathologies, but a major issue in this field is the discovery of isoform-selective compounds, owing to the wide distribution of these proteins into the central and peripheral nervous systems, heart and other peripheral tissues. This survey is focused on the compounds that have been shown, or have been designed, to interact with HCN channels and on their binding sites, with the aim to summarize current knowledge and possibly to unveil useful information to design new potent and selective modulators.

show abstract

Section: Substances That Have Been Shown To Modulate Hcn Channel Actimentioning

confidence: 99%

Section: The Location Of the Interaction Site(s)mentioning

confidence: 99%

HCN Channels Modulators: The Need for Selectivity

Romanelli

Sartiani²,

Masi³

et al. 2016

CTMC

View full text Add to dashboard Cite

show abstract

“…After application of drug for 5 min, cells were restarted activating, then a prominent inhibition of hHCN4 current appeared at the initial phase suggesting that acehytisine have bound to extracellular domain at close state of the channel. In relation to these results, it is note-worthy that these actions are different from that of other I f blockers, zatebradine and amiodarone, which enter the binding site requiring channel opening (Van Bogaert and Pittoors, 2003;Bucchi et al, 2007;Fan et al, 2011). We speculate that acehytisine have been bound to the extracellular domain at close state of the channel.…”

Section: Discussionmentioning

confidence: 55%

“…These interesting findings indicate that acehytisine may be a potential multi-ion channel blocker, just as amiodarone (Fan et al, 2011), a widely applied antiarrhythmic drug.…”

Section: Discussionmentioning

confidence: 96%

Blocking effects of acehytisine on pacemaker currents (If) in sinoatrial node cells and human HCN4 channels expressed in Xenopus laevis oocytes

Fan

Chen

Xing

et al. 2012

Journal of Ethnopharmacology

Self Cite

View full text Add to dashboard Cite

“…Furthermore, studies91,92 have observed that amiodarone and other antiarrhythmic drugs were able to exert their pharmacological action even by interacting with HCN channels of the heart: in particular, amiodarone and bepridil were able to inhibit HCN4 channels of HEK 293 cells at their therapeutic concentrations 91…”

Section: Future Developmentmentioning

confidence: 99%

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Scicchitano¹,

Cortese²,

Ricci³

et al. 2014

DDDT

View full text Add to dashboard Cite

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

show abstract

Novel electropharmacological activity of amiodarone on human HCN channels heterologously expressed in the Xenopus oocytes

Cited by 8 publications

References 37 publications

HCN Channels Modulators: The Need for Selectivity

HCN Channels Modulators: The Need for Selectivity

Blocking effects of acehytisine on pacemaker currents (If) in sinoatrial node cells and human HCN4 channels expressed in Xenopus laevis oocytes

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Contact Info

Product

Resources

About