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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
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001-es BibID:	BIBFORM030338
035-os BibID:	(WoS)A1996UY14300002 (Scopus)0029798762 (PMID)8842570
Első szerző:	Nánási Péter Pál (élettanász)
Cím:	Electrical restitution in diseased human ventricular myocardium / Péter P. Nanasi, Andras Varro, Csaba Pankucsi, Péter Homolay, Timothy K. Knilans, László Kovacs, Gyula J. Papp, David A. Lathrop
Dátum:	1996
ISSN:	0144-5979
Megjegyzések:	Action potential configuration and electrical restitution were studied in diseased human ventricular muscle by comparing the characteristics of hypertrophic (HYP) and dilated (DIL) human ventricular preparations. Conventional microelectrode techniques were used to evaluate action potentials evoked at increasingly longer diastolic intervals, The steady-state action potential duration (APD(90)) was significantly longer in DIL than in HYP preparations (393+/-5 ms, n=4 and 296+/-11 ms, n=4, respectively; P<0.001, mean+/-SEM). In the dilated preparations studied at long diastolic intervals, the initial period of rapid repolarization (phase 1) was absent, and the rate of final repolarization (phase 3) was reduced. Electrical restitution relations in these preparations were fitted as the sum of two exponentials, The time constant of the fast component was significantly longer in DIL than in HYP preparations (242+/-9 ms and 121+/-4 ms, respectively; P<0.001). No difference was observed in the time constants for the slow component of restitution in the two groups. Electrical restitution was also studied in single human ventricular myocytes by using patch clamp techniques. The initial 600 ms period of restitution was fitted in these cells to a monoexponential function. The time constant for this period of the restitution relation was significantly longer, while the estimated amplitude of this early rising phase was significantly lower in human cells obtained from DIL hearts than the respective parameters obtained in the healthy canine and guinea pig cells also examined, The observed changes in the restitution kinetics of the dilated human heart are, likely, the consequence of alterations in the ionic currents that underlie the cardiac action potential.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk egyetemen (Magyarországon) készült közlemény
Megjelenés:	Clinical Physiology. - 16 : 4 (1996), p. 339-351. -
További szerzők:	Varró András (1954-) (farmakológus, klinikai farmakológus) Pankucsi Csaba (farmakológus) Homolay Péter (1947-1999) (mellkassebész, szívsebész) Knilans, Timothy K. Kovács László (1939-) (élettanász) Papp Gy. Julius (Szeged) Lathrop, David A.
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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