| Autor: |
Kawakami S; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University., Takada K; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University., Aimoto M; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University., Nagasawa Y; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University., Kusakabe T; Department of Organic Chemistry, Faculty of Pharmaceutical Sciences, Toho University., Kato K; Department of Organic Chemistry, Faculty of Pharmaceutical Sciences, Toho University., Takahara A; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University. |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2023; Vol. 46 (8), pp. 1120-1127. |
| DOI: |
10.1248/bpb.b23-00202 |
| Abstrakt: |
To clarify the pharmacological properties of the Na + /Ca 2+ exchanger (NCX) inhibitor SEA0400 as an antiarrhythmic agent, we assessed its effects on rapid component of delayed rectifier K + current (I Kr ) blocker-induced torsade de pointes (TdP) in isoflurane-anesthetized rabbits. Atrioventricular block was induced in rabbits using a catheter ablation technique, and the monophasic action potential (MAP) of the right ventricle was measured under electrical pacing at 60 beats/min. In non-treated control animals, intravenous administration of low-dose (0.3 mg/kg) or high-dose nifekalant (3 mg/kg) prolonged the MAP duration (MAP 90 ) by 113 ± 11 ms (n = 5) and 237 ± 39 ms (n = 5), respectively, where TdP was induced in 1/5 animals treated with a low dose and in 3/5 animals treated with a high dose of nifekalant. In SEA0400-treated animals, low- and high-dose nifekalant prolonged the MAP 90 by 65 ± 13 ms (n = 5) and 230 ± 20 ms (n = 5), respectively. No TdP was induced by the low dose but 1/5 animals treated with a high dose of nifekalant developed TdP. In verapamil-treated animals, low-dose and high-dose nifekalant prolonged MAP 90 by 50 ± 12 ms (n = 5) and 147 ± 30 ms (n = 5), respectively, without inducing TdP. These results suggest that SEA0400 has the potential to inhibit low-dose nifekalant-induced TdP by suppressing the MAP-prolonging action of nifekalant, whereas the drug inhibited high-dose nifekalant-induced TdP without affecting the MAP-prolonging action of nifekalant. This may reveal that, in contrast to verapamil, the antiarrhythmic effects of SEA0400 on I Kr blocker-induced TdP may be multifaceted, depending on the severity of the proarrhythmogenic conditions present. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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