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New insights into the effects of organometallic ruthenium complexes on nicotinic acetylcholine receptors [Elektronski vir]Trobec, Tomaž ...Nicotinic acetylcholine receptors (nAChRs) are expressed in excitable and non-excitable cells of the organism. Extensive studies suggest that nAChR ligands have therapeutic potential, notably for ... neurological and psychiatric disorders. Organometallic ruthenium complexes are known to inhibit several medically important enzymes such as cholinesterases. In addition, they can also interact with muscle- and neuronal-subtype nAChRs. The present study aimed to investigate the direct effects of three organometallic ruthenium complexes, [(η6-p-cymene)Ru(II)(5-nitro-1,10-phenanthroline)Cl]Cl (C1-Cl), [(η6-p-cymene)Ru(II)(1-hydroxypyridine-2(1H)-thionato)Cl] (C1a) and [(η6-p-cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1H)-thionato)pta]PF6 (C1), on muscle-subtype (Torpedo) nAChRs and on the two most abundant human neuronal-subtype nAChRs in the CNS (α4β2 and α7) expressed in Xenopus laevis oocytes, using the two-electrode voltage-clamp. The results show that none of the three compounds had agonistic activity on any of the nAChR subtypes studied. In contrast, C1-Cl reversibly blocked Torpedo nAChR (half-reduction of ACh-evoked peak current amplitude by 332 nM of compound). When tested at 10 μM, C1-Cl was statistically more potent to inhibit TorpedonAChR than α4β2 and α7 nAChRs. Similar results of C1 effects were obtained on Torpedo and α4β2 nAChRs, while no action of the compound was detected on α7 nAChRs. Finally, the effects of C1a were statistically similar on the three nAChR subtypes but, in contrast to C1-Cl and C1, the inhibition was hardly reversible. These results, together with our previous studies on isolated mouse neuromuscular preparations, strongly suggest that C1-Cl is, among the three compounds studied, the only molecule that could be used as a potential myorelaxant drug.Source: Chemico-Biological Interactions [Elektronski vir] (Vol. 402, [article no.] 111213, 2024, str. 1-7)Type of material - e-articlePublish date - 2024Language - englishCOBISS.SI-ID - 205689347
Author
Trobec, Tomaž |
Lamassiaude, Nicolas |
Benoit, Evelyne |
Žužek, Monika C. |
Sepčić, Kristina |
Kladnik, Jerneja |
Turel, Iztok |
Romulo, Araoz |
Frangež, Robert
Topics
organometallic ruthenium complexes |
nicotinic acetylcholine receptors |
nicotinic antagonists |
electrophysiology |
two-electrode voltage-clamp technique
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Trobec, Tomaž | 51852 |
Lamassiaude, Nicolas | ![]() |
Benoit, Evelyne | ![]() |
Žužek, Monika C. | 22588 |
Sepčić, Kristina | 15328 |
Kladnik, Jerneja | 39077 |
Turel, Iztok | 11053 |
Romulo, Araoz | ![]() |
Frangež, Robert | 12449 |
Source: Personal bibliographies
and: SICRIS
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