Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- 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
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.
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J Clin Psychopharmacol. 1997 Aug;17(4):318-21 PubMed
Br J Pharmacol. 1986 Nov;89(3):603-12 PubMed
Chest. 1977 Feb;71(2):210-3 PubMed
J Pharmacol Exp Ther. 1999 Aug;290(2):515-23 PubMed
J Physiol. 1999 Jul 15;518 ( Pt 2):371-84 PubMed
Am J Cardiol. 1997 Jan 15;79(2):242-5 PubMed
Ann Clin Biochem. 1998 Mar;35 ( Pt 2):261-7 PubMed
Drug Chem Toxicol. 2005;28(3):303-13 PubMed
Pharm Res. 2006 Jun;23(6):1133-43 PubMed
Med Biol Eng Comput. 2004 Mar;42(2):151-7 PubMed
Psychopharmacology (Berl). 1994 Feb;114(1):24-30 PubMed
J Am Coll Cardiol. 1992 Nov 15;20(6):1391-6 PubMed
Am J Med. 1979 Aug;67(2):353-7 PubMed
Gen Physiol Biophys. 2005 Sep;24(3):311-25 PubMed
J Pharmacol Exp Ther. 1990 Dec;255(3):1038-46 PubMed
Clin Pharmacol Ther. 1989 Jul;46(1):78-81 PubMed
Br J Pharmacol. 1998 Oct;125(4):659-66 PubMed
Eur Biophys J. 2001 Dec;30(7):500-14 PubMed
Clin Pharmacol Ther. 1996 Jul;60(1):41-7 PubMed
Clin Pharmacol Ther. 1997 Sep;62(3):334-47 PubMed
Gen Physiol Biophys. 2005 Mar;24(1):27-45 PubMed
Acta Pharmacol Toxicol (Copenh). 1969;27(2):183-92 PubMed
Mol Pharmacol. 1992 Feb;41(2):322-30 PubMed
Br J Pharmacol. 1995 May;115(2):335-43 PubMed
Eur J Pharmacol. 2006 Nov 21;550(1-3):15-23 PubMed
Pflugers Arch. 1994 Aug;428(1):84-90 PubMed
Circulation. 2002 Mar 12;105(10):1208-13 PubMed
Eur J Pharmacol. 1984 Oct 1;105(1-2):23-31 PubMed
Cardiovasc Res. 1993 Sep;27(9):1662-9 PubMed
