CCL

Összesen 3 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM030258
035-os BibID:WOS:000181565400020
Első szerző:Magyar János (élettanász)
Cím:Differential effects of fluoxetine enantiomers in mammalian neural and cardiac tissues / János Magyar, Zoltán Rusznák, Csaba Harasztosi, Ágnes Körtvély, Pál Pacher, Tamás Bányász, Csaba Pankucsi, László Kovács, Géza Szűcs, Péter P. Nánási, Valéria Kecskeméti
Dátum:2003
ISSN:1107-3756
Megjegyzések:Racemic fluoxetine is a widely used SSRI antidepressant compound having also anticonvulsant effect. In addition, it was shown that it blocked several types of voltage gated ion channels including neural and cardiac calcium channels. In the present study the effects of enantiomers of fluoxetine (R(-)-fluoxetine and S(+)-fluoxetine) were compared on neuronal and cardiac voltage-gated Ca2+ channels using the whole cell configuration of patch clamp techniques, and the anticonvulsant action of these enantiomers was also evaluated in a mouse epilepsy model. In isolated pyramidal neurons of the dorsal cochlear nucleus of the rat the effect of fluoxetine (S(+), R(-) and racemic) was studied on the Ca2+ channels by measuring peak Ba2+ current during ramp depolarizations. All forms of fluoxetine reduced the Ba2+ current of the pyramidal cells in a concentration-dependent manner, with a K, value of 22.3 +/- 3.6 muM for racemic fluoxetine. This value of K, was higher by one order of magnitude than found in cardiac myocytes with fluoxetine enantiomers (2.4 +/- 0.1 and 2.8 +/- 0.2 muM). Difference between the effects of the two enantiomers on neuronal Ba2+, current was observed only at 5 muM concentration: R(-)-fluoxetine inhibited 28 +/- 3% of the peak current, while S(+)-fluoxetine reduced the current by 18 +/- 2% (n=13, P<0.05). In voltage clamped canine ventricular cardiomyocytes both enantiomers of fluoxetine caused a reversible concentration-dependent block of the peak Ca2+ current measured at 0 mV. Significant differences between the two enantiomers in this blocking effect was observed at low concentrations only: S(+)-fluoxetine caused a higher degree of block than R(-)-fluoxetine (56.3 +/- 2.2% versus 49.1 +/- 2.2% and 95.5 +/- 0.9% versus 84.5 +/- 3.1% block with 3 and 10 &mu;M S(+) and R(-)-fluoxetine, respectively, P<0.05, n=5). Studied in current clamp mode, micromolar concentrations of fluoxetine shortened action potential duration of isolated ventricular cells, while higher concentrations also suppressed maximum velocity of depolarization and action potential amplitude. This shortening effect was significantly greater in the case of S(+) than R(-)-fluoxetine at 1 and 3 muM concentrations, whereas no differences in their effects on depolarization were observed. In pentylenetetrazole-induced mouse epilepsy model fluoxetine pretreatment significantly increased the 60 min survival rate, survival duration and seizure latency. These effects were more pronounced with the R(-) than the S(+) enantiomer. The results indicate that fluoxetine exerts much stronger suppressive effect on cardiac than neuronal calcium channels. At micromolar concentrations (between 1 and 10 muM) R(-)-fluoxetine is more effective than the S(+) enantiomer on neuronal, while less effective on cardiac calcium channels. The stronger anticonvulsant effect of the R(-) enantiomer may, at least partially, be explained by these differences. Used as an antidepressant or anticonvulsant drug, less severe cardiac side-effects are anticipated with the R(-) enantiomer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:International Journal of Molecular Medicine. - 11 : 4 (2003), p. 535-542. -
További szerzők:Rusznák Zoltán (1965-) (élettanász) Harasztosi Csaba Körtvély Ágnes Pacher Pál Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Kovács László (1939-) (élettanász) Szűcs Géza (1948-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Kecskeméti Valéria
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM030256
035-os BibID:WOS:000178499200009
Első szerző:Magyar János (élettanász)
Cím:Electrophysiological effects of risperidone in mammalian cardiac cells / János Magyar, Tamás Bányász, Zsolt Bagi, Pál Pacher, Norbert Szentandrássy, László Fülöp, Valéria Kecskeméti, Péter P. Nánási
Dátum:2002
ISSN:0028-1298
Megjegyzések:In this study, the effects of risperidone, the widely used antipsychotic drug, on isolated canine ventricular myocytes and guinea-pig papillary muscles were analyzed using conventional microelectrode and whole cell voltage-clamp techniques. Risperidone concentration-dependently lengthened action potential duration in guinea-pig papillary muscles (EC50=0.29 +/- 0.02 muM) and single canine ventricular myocytes (EC50=0.48 +/- 0.14 muM). This effect was reversible, showed reverse rate dependence, and it was most prominent on the terminal portion of repolarization. No significant effect of risperidone on the resting membrane potential, action potential amplitude or maximum rate of depolarization was observed. In voltage-clamped canine ventricular myocytes risperidone caused concentration-dependent block of the rapid component of the delayed rectifier K+ current (1(Kr)), measured as outward current tails at -40 mV with an IC50 of 0.92 +/- 0.26 muM. Suppression of I-Kr was not associated with changes in activation or deactivation kinetics. High concentration of risperidone (10 muM) suppressed also the slow component of the delayed rectifier K+ current (I-Ks) by 9.6 +/- 1.5% at +50 mV. These effects of risperidone developed rapidly and were readily reversible. Risperidone had no significant effect on the amplitude of other K+ currents (I-K1 and I-to). The inhibition of cardiac I-Kr current by risperidone may explain the cardiac side-effects observed occasionally with the drug. Our results suggest that risperidone displays class III antiarrhythmic properties, and as such, may produce QTc prolongation, especially in patients with long QT syndrome. Therefore, in psychotic patients having also cardiac disorders, ECG control may be suggested during risperidone therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 366 : 4 (2002), p. 350-356. -
További szerzők:Bányász Tamás (1960-) (élettanász) Bagi Zsolt (1974-) (orvos) Pacher Pál Szentandrássy Norbert (1976-) (élettanász) Fülöp László (1976-) (kardiológus) Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM030266
035-os BibID:WOS:000084701100010
Első szerző:Pacher Pál
Cím:Electrophysiological effects of fluoxetine in mammalian cardiac tissues / Pál Pacher, János Magyar, Péter Szigligeti, Tamás Bányász, Csaba Pankucsi, Zsuzsanna Korom, Zoltán Ungvári, Valéria Kecskeméti, Péter P. Nánási
Dátum:2000
ISSN:0028-1298
Megjegyzések:Fluoxetine is a widely used antidepressant compound having selective serotonin reuptake inhibitor properties. In this study, the actions of fluoxetine were analyzed in guinea pig, rat, rabbit and canine ventricular myocardiac preparations using conventional microelectrode and whole cell voltage clamp techniques. Low concentrations of fluoxetine (1-10 mu mol/l) caused significant shortening of action potential duration (APD) and depression of the plateau potential in guinea pig and rabbit papillary muscles and single canine ventricular myocytes. In rat papillary muscle, APD was not affected by fluoxetine (up to 100 mu mol/l), however, the drug decreased the force of contraction with EC50 of 10 mu mol/l. Fluoxetine (10 mu mol/l) also decreased the maximum velocity of depolarization and action potential overshoot in each species studied. At this concentration no effect was observed on the resting membrane potential; high concentration (100 mu mol/l), however, caused depolarization. In voltage clamped canine ventricular myocytes, fluoxetine caused concentration-dependent block of the peak Ca2+ current at 0 mV with EC50 Of 5.4+/-0.94 mu mol/l and Hill coefficient of 1.1+/-0.14 (n=6). In addition, 10 mu mol/l fluoxetine shifted the midpoint of the steady-state inactivation curve of the Ca2+ current from -20.7+/-0.65 to -26.7+/-1 mV (P<0.001, n=8) without changing its slope factor. These effects of fluoxetine developed rapidly and were fully reversible. Fluoxetine did not alter voltage-dependence of activation or time constant for inactivation of I-Ca. Fluoxetine had no effect on the amplitude of K+ currents (I-K1 and I-to). The inhibition of cardiac Ca2+ and Na+ channels by fluoxetine may explain most cardiac side effects observed occasionally with the drug. Our results suggest that fluoxetine may have antiarrhythmic (class I + IV type), as well as proarrhythmic properties (due to impairment of atrioventricular or intraventricular conduction and shortening of repolarization). Therefore, in depressed patients with cardiac disorders, ECG control may be suggested during fluoxetine therapy.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 361 : 1 (2000), p. 67-73. -
További szerzők:Magyar János (1961-) (élettanász) Szigligeti Péter Bányász Tamás (1960-) (élettanász) Pankucsi Csaba (farmakológus) Korom Zsuzsanna Ungvári Zoltán Kecskeméti Valéria Nánási Péter Pál (1956-) (élettanász)
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1