Találati lista | Tudóstér

001-es BibID:	BIBFORM049492
Első szerző:	Hegyi Bence (élettanász)
Cím:	Selectivity problems with drugs acting on cardiac Na+ and Ca2+ channels / Bence Hegyi, István Komáromi, Péter P. Nánási, Norbert Szentandrássy
Dátum:	2013
ISSN:	0929-8673
Megjegyzések:	With the increase of our knowledge on cardioactive agents it comes more and more clear that practically none of the currently used compounds shows absolute selectivity to one or another ion channel type. This is particularly true for Na(+) and Ca(2+) channel modulators, which are widely applied in the clinical practice and biomedical research. The best example might be probably the marine guanidine poison tetrodotoxin, which has long been considered as a selective Na(+) channel blocker, while recently it turned out to effectively inhibit cardiac Ca(2+) currents as well. In the present study the cross actions observed between the effects of various blockers of Na(+) channels (such as toxin inhibitors, class I antiarrhythmics and local anesthetics) and Ca(2+) channels (like phenylalkylamines, dihydropyridine compounds, diltiazem and mibefradil) are overviewed in light of the known details of the respective channel structures. Similarly, activators of Na(+) channels, including veratridine and batrachotoxin, are also compared. The binding of tetrodotoxin and saxitoxin to Cav1.2 and Nav1.5 channel proteins is presented by construction of theoretical models to reveal common structures in their pore forming regions to explain cross reactions. Since these four domain channels can be traced back to a common ancestor, a close similarity in their structure can well be demonstrated. Thus, the poor selectivity of agents acting on cardiac Na(+) and Ca(2+) channels is a consequence of evolution. As a conclusion, since the limited selectivity is an intrinsic property of drug receptors, it has to be taken into account when designing new cardioactive compounds for either medical therapy or experimental research in the future.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Na+ channels Ca2+ channels ion selectivity cardioactive drugs channel structures tetrodotoxin Doktori iskola
Megjelenés:	Current Medicinal Chemistry. - 20 : 20 (2013), p. 2552-2571. -
További szerzők:	Komáromi István (1957-) (vegyész, molekuláris biológus, biokémikus) Nánási Péter Pál (1956-) (élettanász) Szentandrássy Norbert (1976-) (élettanász)
Pályázati támogatás:	TÁMOP-4.2.2.A-11/1/KONV-2012-0045 TÁMOP Élettan Kutatócsoport K100151 OTKA PD101171 OTKA K101196 OTKA CNK-77855 OTKA TÁMOP-4.2.2/B-10/1-2010-0024 TÁMOP Molekuláris Orvostudomány Doktori Iskola
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon:

001-es BibID:	BIBFORM077899
035-os BibID:	(PMID)29278207 (WoS)000432247500002 (Scopus)85048878557
Első szerző:	Nánási Péter Pál ifj. (sejtbiológus)
Cím:	Omecamtiv Mecarbil : a Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results / Péter Nánási Jr., István Komáromi, Marta Gaburjakova, János Almássy
Dátum:	2018
ISSN:	0929-8673
Megjegyzések:	Abstract: Background: Clinical treatment of heart failure is still suffering from limited efficacy and unfavorable side effects. The recently developed group of agents, the myosin motor activators, act directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. The lead molecule, omecamtiv mecarbil is now in human 3 stage. In addition tothe promising clinical data published so far, there are new in vitro results indicating that the effect of omecamtiv mecarbil on contractility is rate-dependent. Furthermore, omecamtiv mecarbilwas shown to activate cardiac ryanodine receptors, an effect that may carry proarrhythmic risk. Methods: These new results, together with the controversial effects of the drug on cardiac oxygen consumption, are critically discussed in this review in light of the current literature on omecamtiv mecarbil. Results: In therapeutically relevant concentrations the beneficial inotropic effect of the agent isnot likely affected by these new results - in accordance with the good clinical data. At supratherapeutic concentrations, however, activation of cardiac ryanodine receptors may increasearrhythmia propensity, and the stronger effect on diastolic than systolic cell shortening, observed at higher pacing frequencies, may decrease or offset the inotropic effect of omecamtivmecarbil. Conclusion: Further studies with definitely supratherapeutical concentrations of omecamtivmecarbil should be designed to map the actual risk of these potentially harmful side-effects.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Heart failure inotropic agents myosin activators Omecamtiv mecarbil Ryanodine receptor Cytosolic Ca 2+
Megjelenés:	Current Medicinal Chemistry. - 25 : 15 (2018), p. 1720-1728. -
További szerzők:	Komáromi István (1957-) (vegyész, molekuláris biológus, biokémikus) Gaburjakova, Marta Almássy János (1981-) (élettanász, biológus, angol-magyar szakfordító)
Pályázati támogatás:	NKFIH PD112199 NKFIH Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences MTA Szodoray Scholarship of the University of Debrecen Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: