Inhibition of cardiac Na<sup>+</sup>
 current by primaquine

Orta-Salazar, Gerardo; Bouchard, Ron A.; Morales-Salgado, Fernando; Salinas-Stefanon, Eduardo M.

doi:10.1038/sj.bjp.0704460

Cited by 26 publications

(21 citation statements)

References 42 publications

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“…The most important analogue of these was primaquine. Primaquine reportedly acts by blocking the inward sodium current and slowing the upstroke of the action potential (Bass et al, 1972;Orta-Salazar et al, 2002). Till date the effects of primaquine on hERG channel has not been mapped.…”

Section: Introductionmentioning

confidence: 95%

Blockade of hERG K+ channel by antimalarial drug, primaquine

et al. 2010

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Lengthening of the Q-T interval and proarrhythmia are adverse effects associated with antimalarial agents. Also, lengthening of the Q-T interval is a definite outcome when patients are administered with an overdose of primaquine. Inhibition of potassium current I (Kr) and resultant QT prolongation is suggested as the reason behind drug-induced arrhythmias. The present study investigated the molecular mechanisms of voltage-dependent inhibition of human Ether-a-go-go Related Gene (hERG) delayed rectifier K(+) channels expressed in HEK-293 cells by primaquine. Primaquine inhibited hERG current in a concentration-dependent manner with the half-maximal inhibitory concentration (IC(50)) of 21.5 microM. The voltage-dependent inhibition of hERG current resulted in the activation curve to be shifted to a negative voltage after primaquine exposure in a dose-dependent manner. Blockade of hERG by primaquine was also found to be time-dependent, occurring rather rapidly. Blockade of wild-type hERG channel by primaquine was similar to those of both the S6 residue hERG mutants (F656A and Y652A) and the pore region mutants (T623A). In conclusion, these results indicate that primaquine preferentially inhibits the hERG potassium channel, but blockade of hERG channel by primaquine may not be related to the S6 residue or the pore region, but may be induced through other pathways such as binding other region or effect by drug binding receptor which indicates a need for further exploration.

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Section: Introductionmentioning

confidence: 95%

Blockade of hERG K+ channel by antimalarial drug, primaquine

et al. 2010

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“…PQ was found to block the cardiac channels with high affinity, exhibiting high selectivity for the Na þ channel blockade in comparison to the blockade of the K þ cardiac channel [106].…”

Section: Other Biological Effects Of Pqmentioning

confidence: 99%

Primaquine revisited six decades after its discovery

Vale¹,

Moreira²,

Gomes³

2009

European Journal of Medicinal Chemistry

322

308

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“…V max , APA, and OS are formed mainly by 0 phase depolarization. Because regional differences of I to channels do not affect depolarization of ventricular myocytes, and thus, there are no significant differences of V max , APA, and OS in epicardial, mid-myocardial and endocardial myocytes [25].…”

Section: Discussionmentioning

confidence: 99%

Increasing DHA and EPA Concentrations Prolong Action Potential Durations and Reduce Transient Outward Potassium Currents in Rat Ventricular Myocytes

Wang

et al. 2010

Lipids

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The goal of this study was to determine the mechanisms of n-3 polyunsaturated fatty acids (n-3 PUFA) on anti-arrhythmias and prevention of sudden death. The calcium-tolerant Sprague-Dawley rat ventricular myocytes were isolated by enzyme digestion. Effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on action potentials and transient outward potassium currents (I (to)) of epicardial ventricular myocytes were investigated using whole-cell patch clamp techniques. Action potential durations (APDs) and I (to) were observed in different concentrations of DHA and EPA. APD(25), APD(50), and APD(90) with 0.1 μmol/L DHA and EPA were prolonged less than 15% and 10%. However, APDs were prolonged in concentration-dependent manners when DHA and EPA were more than 1 μmol/L. APD(25), APD(50), and APD(90) were 7.7 ± 2.0, 21.2 ± 3.5, and 100.1 ± 9.8 ms respectively with 10 μmol/L DHA, and 7.2 ± 2.5, 12.8 ± 4.2, and 70.5 ± 10.7 ms respectively with 10 μmol/L EPA. I (to) currents were gradually reduced with the increased concentrations of DHA and EPA from 1 to 100 μmol/L, and their half-inhibited concentrations were 2.3 ± 0.2 and 3.8 ± 0.6 μmol/L. The results showed APDs were prolonged and I (to) current densities were gradually reduced with the increased concentrations of DHA and EPA. The anti-arrhythmia mechanisms of n-3 PUFA are complex, however, the effects of n-3 PUFA on action potentials and I (to) may be one of the important mechanisms.

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Inhibition of cardiac Na⁺ current by primaquine

Cited by 26 publications

References 42 publications

Blockade of hERG K+ channel by antimalarial drug, primaquine

Blockade of hERG K+ channel by antimalarial drug, primaquine

Primaquine revisited six decades after its discovery

Increasing DHA and EPA Concentrations Prolong Action Potential Durations and Reduce Transient Outward Potassium Currents in Rat Ventricular Myocytes

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Inhibition of cardiac Na+ current by primaquine

Cited by 26 publications

References 42 publications

Blockade of hERG K+ channel by antimalarial drug, primaquine

Blockade of hERG K+ channel by antimalarial drug, primaquine

Primaquine revisited six decades after its discovery

Increasing DHA and EPA Concentrations Prolong Action Potential Durations and Reduce Transient Outward Potassium Currents in Rat Ventricular Myocytes

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Product

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Inhibition of cardiac Na⁺ current by primaquine