Találati lista | Tudóstér

001-es BibID:	BIBFORM018458
Első szerző:	Kecskeméti Valéria
Cím:	Norfluoxetine and fluoxetine have similar anticonvulsant and Ca channel blocking potencies / Kecskeméti V., Rusznák Z., Riba P., Pál B., Wagner R., Harasztosi C., Nánási P. P., Szűcs G.
Dátum:	2005
ISSN:	0361-9230
Megjegyzések:	Norfluoxetine is the most important active metabolite of the widely used antidepressant fluoxetine but little is known about its pharmacological actions. In this study the anticonvulsant actions of norfluoxetine and fluoxetine were studied and compared to those of phenytoin and clonazepam in pentylenetetrazol-induced mouse epilepsy models. Pretreatment with fluoxetine or norfluoxetine (20 mg/kg s.c.), as well as phenytoin (30 mg/kg s.c.) and clonazepam (0.1 mg/kg s.c.) significantly increased both the rate and duration of survival, demonstratinga significant protective effect against pentylenetetrazol-induced epilepsy. These effects of norfluoxetine were similar to those of fluoxetine. According to the calculated combined protection scores, both norfluoxetine and fluoxetine were effective from the concentration of 10 mg/kg,while the highest protective action was observed with clonazepam. Effects of norfluoxetine and fluoxetine on voltage-gated Ca2+ channels were evaluated by measuring peak Ba2+ current flowing through the Ca2+ channels upon depolarization using whole cell voltage clamp in enzymatically isolated rat cochlear neurons. The current was reduced equally in a concentration-dependent manner by norfluoxetine (EC50 = 20.4?2.7M, Hill coefficient = 0.86?0.1) and fluoxetine(EC50 = 22.3?3.6M, Hill coefficient = 0.87?0.1). It was concluded that the efficacy of the two compounds in neuronal tissues was equal, either in preventing seizure activity or in blockingthe neuronal Ca2+ channels.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Fluoxetine Norfluoxetine Anticonvulsants Neuronal Ca2+ currents Voltage clamp
Megjelenés:	Brain Research Bulletin. - 67 : 1-2 (2005), p. 126-132. -
További szerzők:	Rusznák Zoltán (1965-) (élettanász) Riba Pál Pál Balázs (1975-) (élettanász) Wagner Róbert Harasztosi Csaba Nánási Péter Pál (1956-) (élettanász) Szűcs Géza (1948-) (élettanász)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

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 μM 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:
Saját polcon: