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1.

001-es BibID:BIBFORM030274
035-os BibID:WOS:000079560700007
Első szerző:Bányász Tamás (élettanász)
Cím:EGIS-7229, the new combined class III antiarrhythmic agent : lack of EAD inducing effect / Tamás Bányász, János Magyar, András Varró, Anikó Kovács, Ildikó Gyönös, Gábor Szénási, Péter P. Nánási
Dátum:1999
ISSN:0306-3623
Megjegyzések:EGIS-7229 is a novel antiarrhythmic candidate having multiple mechanisms of action with class III predominance. In this study, the effects of EGIS-7229 and sotalol on action potential duration (APD) and incidence of early afterdepolarizations (EADs) were studied and compared in rabbit papillary muscle by using conventional microelectrode techniques. In control bathing solution, both drugs increased APD in a concentration-dependent manner; however, the prolongation of APD was greater with sotalol than with EGIS-7229 when the same drug concentrations were compared. EAD developed in 3 of the 11 preparations (27%) bathed with a solution containing 3.6 mmol/l CsCl + 2 mmol/l KCl within the first 120 min of superfusion. The addition of 100 mu mol/l sotalol to this superfusate increased the incidence of EAD to 83% (10 from 12), whereas the addition of the same concentration of EGIS-7229 prevented the development of EAD in all of the 9 preparations studied. These differences in incidence of EAD are likely attributable to differences in drug-induced increases of APD-50 in the presence of CsCl. Prolongation of APD-90 showed less correlation with incidence of EAD than changes in APD-50. On the basis of these in vitro results, high concentrations of EGIS-7229 cannot be expected to be torsadogenic in vivo-in contrast with sotalol-presumably owing to the combined class III + IV activity of the compound. (C) 1999 Elsevier Science Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology. - 32 : 3 (1999), p. 329-333. -
További szerzők:Magyar János (1961-) (élettanász) Varró András (1954-) (farmakológus, klinikai farmakológus) Kovács Anikó Gyönös Ildikó Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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2.

001-es BibID:BIBFORM030254
Első szerző:Kovács Anikó
Cím:Effects of EGIS-7229 (S 21407), a novel class III antiarrhythmic drug, on myocardial refractoriness to electrical stimulation in vivo and in vitro / Anikó Kovács, Ildikó Gyönös, János Magyar, Tamás Bányász, Péter P. Nánási, Michael Spedding, Gábor Szénási
Dátum:2001
ISSN:0160-2446
Megjegyzések:The I-Kr blocker EGIS-7229 (S-21407), displays class Ib and class IV effects that may alter its pharmacologic profile compared with those of pure I-Kr blockers. Therefore, the concentration- and frequency-dependent effects of EGIS-7229, and of the I-Kr blockers d,l-sotalol and dofetilide, on the effective refractory period (ERP) were measured in isolated right ventricular papillary muscle of the rabbit in vitro. The effects of these drugs on right ventricular fibrillation threshold (RVFT) at increasing intravenous doses were also determined in anesthetized cats. Dofetilide and d,l-sotalol increased ERP in a concentration-dependent manner (dofetilide: 3-100 nM; d,l-sotalol: 3-100 muM) with strong reverse frequency dependence at high concentrations. EGIS-7229 concentration dependently lengthened ERP at 1-30 muM. Its effect on ERP was clearly reverse frequency dependent at 3 muM, but this feature of the drug diminished at 10 muM and was not apparent at 30 muM The effect of EGIS-7229 (30 muM) on ERP was devoid of reverse frequency dependence as it was more effective (31%) than dofetilide (16 %) at high-pacing rate (3 Hz), whereas it was less effective (50%) than dofetilide (70%) at slow-pacing rate (1 Hz). Reverse frequency-dependent ERP effect of dofetilide (100 nM) was similarly abolished by the addition of lidocaine (30 muM). EGIS-7229 (1-8 mg/kg iv), d,l-sotalol (1-8 mg/kg iv), and dofetilide (10-80 mug/kg iv) caused a dose-dependent increase in RVFT. The minimum effective dose of d,l-sotalol and EGIS-7229 was 1 and 2 mg/kg, respectively. whereas that of dofetilide was 10 mug/kg. EGIS-7229 induced a smaller peak effect in RVFT than sotalol or dofetilide. In conclusion, EGIS-7229 markedly increased refractoriness to electrical stimulation in vitro and in vivo. Compared with pure I-Kr blockers, the benefits of EGIS-7229 seem to be a greater lengthening of effective refractory period at rapid stimulation rates, suggesting a strong antiarrhythmic action, and a smaller effect at slow stimulation rates, suggesting low potential to induce early afterdepolarizations.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Journal of Cardiovascular Pharmacology. - 37 : 1 (2001), p. 78-88. -
További szerzők:Gyönös Ildikó Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Spedding, Michael Szénási Gábor
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3.

001-es BibID:BIBFORM030278
035-os BibID:WOS:A1997WN91400013
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated mammalian and human cardiac tissues / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, András Varró, Gábor Szénási, Péter P. Nánási
Dátum:1997
ISSN:0028-1298
Megjegyzések:The cellular electrophysiological effects of EGIS-7229 (5-chlor-4-[N-(3,4-dimethoxy-phenyl-ethyl)- amino-propylamino]-3(2H)-pyridazinone fumarate), a novel antiarrhythmic agent, was studied using conventional microelectrode techniques in canine cardiac Purkinje fibers and papillary muscle preparations obtained from man, rabbits and guinea pigs. Low concentration of EGIS-7229 (3 mu mol/l) selectively lengthened action potential duration (both APD(50) and APD(90)) in all preparations. The effect of higher concentrations (30-100 mu mol/l) of EGIS-7229 on action potential duration was variable depending on the preparation studied: in rabbit and human papillary muscles both APD(50) and APD(90) were lengthened, in canine Purkinje fibers APD(90) was lengthened but APD(50) was shortened, while in guinea pig papillary muscles both APD(50) and APD(90) were shortened by high concentrations of the drug. At these higher concentrations EGIS-7229 also decreased the maximum velocity of action potential upstroke (V-max) and depressed the plateau of action potentials without affecting the resting membrane potential or action potential amplitude. Both reduction of V-max and lengthening of APD were frequency dependent. The former effect was more prominent at higher pacing frequencies, while the latter was more pronounced at lower driving rates. In guinea pig papillary muscle, the time constant of recovery from V-max block was 719 +/- 33 ms (n = 18) and the rate of onset of the block was 1.81 +/- 0.06 AP(-1) (n = 16) in the presence of 100 mu mol/l EGIS-7229. EGIS-7229 had a complex action on refractoriness in guinea pig papillary muscles: ERP was lengthened at low concentrations (3 to 10 mu mol/l), unchanged at 30 mu mol/l and shortened at 100 mu mol/l. The ratio of ERP/APD(90) however, was significantly increased at concentrations higher than 3 mu mol/l. In canine Purkinje fiber when the delayed rectifier K current (I-K) was blocked by d-sotalol (60 mu mol/l) and APD was shortened back to its control value by additional application of nicorandil (15 mu mol/l), APD was not affected by 3 mu mol/l but was shortened by 30 mu mol/l of EGIS-7229. 100 mu mol/l EGIS-7229 shortened APD in guinea pig papillary muscle. This effect of EGIS-7229 was effectively prevented by nifedipine pretreatment (10 mu mol/l). In this preparation, EGIS-7229 also decreased the V-max of the slow action potential, evoked in the presence of 20 mmol/l external K+ plus 0.5 mmol/l Ba2+. It is likely that EGIS-7229 at low concentrations blocks I-K in human, canine, rabbit and guinea pig cardiac preparations, but at higher concentrations also inhibits Ca and Na currents. Therefore, EGIS-7229 appears to carry mixed class III, IV and IB antiarrhythmic properties.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Naunyn-Schmiedebergs Archives of Pharmacology. - 355 : 3 (1997), p. 398-405. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Varró András (1954-) (farmakológus, klinikai farmakológus) Szénási Gábor Nánási Péter Pál (1956-) (élettanász)
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4.

001-es BibID:BIBFORM030277
035-os BibID:WOS:A1997XM42500024
Első szerző:Pankucsi Csaba (farmakológus)
Cím:Electrophysiological effects of EGIS-7229, a new antiarrhythmic agent, in isolated guinea pig papillary muscle / Csaba Pankucsi, Tamás Bányász, János Magyar, Ildikó Gyönös, Anikó Kovács, Gábor Szénási, András Varró, Péter P. Nánási
Dátum:1997
ISSN:0306-3623
Megjegyzések:1. The cellular electrophysiological effects of EGIS-7229, a novel antiarrhythmic agent, were studied in guinea pig papillary muscles with the use of conventional microelectrode techniques. 2. The drug had a concentration-dependent biphasic effect on action potential duration (APD). APD was significantly lengthened at low concentration (3 mu mol/l), whereas it was shortened at concentrations higher than 10 mu mol/l. 3. At concentrations higher than 10 mu mol/l, the drug decreased the maximum velocity of action potential upstroke (V-max), the force of contraction, and altered the restitution kinetics of APD. 4. The effect of EGIS-7229 on V-max was frequency dependent; it was most prominent at short pacing cycle lengths (use-dependent block). 5. On the basis of present results, EGIS-7229 appears to carry mixed class I and class III characteristics, Class III properties are present at low concentrations, whereas, at higher concentrations, class I actions may be predominant. GEN PHARMAC 29;2:275-280, 1997. (C) 1997 Elsevier Science Inc.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:General Pharmacology 29 : 2 (1997), p. 275-280. -
További szerzők:Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Gyönös Ildikó Kovács Anikó Szénási Gábor Varró András (1954-) (farmakológus, klinikai farmakológus) Nánási Péter Pál (1956-) (élettanász)
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