Antipsychotic drug perphenazine belongs to the phenothiazine group commonly reported to induce ECG changes and tachyarrhythmias. Data about its effect on ionic membrane currents in cardiomyocytes are missing. We analyzed the effect of perphenazine (0.1-100 microM) on fast sodium current I (Na) and transient outward potassium current I (to) in enzymatically isolated rat right ventricular myocytes by the whole-cell patch-clamp technique at room temperature. Perphenazine reversibly blocked I (Na) (reducing its amplitude; IC(50) = 1.24 +/- 0.10 microM) and I (to) (accelerating its apparent inactivation with a slight decrease of its amplitude; IC(50) = 38.2 +/- 3.5 microM, evaluated from changes of the time integral). The fast time constant of I (to) inactivation was significantly decreased in a concentration-dependent manner (IC(50) = 30.0 +/- 6.6 microM). Both blocks were use and frequency dependent at 3.3 Hz. We conclude that perphenazine causes concentration-, use-, and frequency-dependent block of I (Na) and I (to) . Computer simulations suggest that perphenazine interacts preferentially with I (Na) channels in inactivated states and with I (to) channels in both open and open-inactivated states.
- MeSH
- antipsychotika aplikace a dávkování toxicita MeSH
- draslíkové kanály účinky léků metabolismus MeSH
- inhibiční koncentrace 50 MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- metoda terčíkového zámku MeSH
- perfenazin aplikace a dávkování toxicita MeSH
- počítačová simulace MeSH
- potkani Wistar MeSH
- sodíkové kanály účinky léků metabolismus MeSH
- srdeční komory cytologie účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antipsychotika MeSH
- draslíkové kanály MeSH
- perfenazin MeSH
- sodíkové kanály MeSH
