Antiarrhythmic effects of newly developed propafenone derivatives
Antiaritmički efekti novosintetisanih derivata propafenona
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It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PV...T. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.
Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na
njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati
propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na
propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto
položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model
na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu
supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje
lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i
paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i
potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka
supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti
da novosint...etisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog
jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i
ispitivanju njihovog antiaritmijskog efekta.
Keywords:
rats / aconitine / experimental arrhythmia / propafenone derivatives / derivati propafenona / eksperimentalna aritmija / pacovi / akonitinSource:
Arhiv za farmaciju, 2022, 72, 4, 392-412Publisher:
- Pharmaceutical Association of Serbia
Funding / projects:
- Development of new technology for production of red wine and diatery supplements reach with polyphenols with cardioprotective effects (RS-31020)
- Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations (RS-172041)
- The Alexander von Humboldt Foundation (Germany).
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Institution/Community
PharmacyTY - JOUR AU - Ivković, Branka AU - Opačić, Dragan AU - Džudović, Boris AU - Crevar, Milkica AU - Gojković-Bukarica, Ljiljana PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4306 AB - It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects. AB - Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i ispitivanju njihovog antiaritmijskog efekta. PB - Pharmaceutical Association of Serbia T2 - Arhiv za farmaciju T1 - Antiarrhythmic effects of newly developed propafenone derivatives T1 - Antiaritmički efekti novosintetisanih derivata propafenona VL - 72 IS - 4 SP - 392 EP - 412 DO - 10.5937/arhfarm72-37114 ER -
@article{ author = "Ivković, Branka and Opačić, Dragan and Džudović, Boris and Crevar, Milkica and Gojković-Bukarica, Ljiljana", year = "2022", abstract = "It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects., Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i ispitivanju njihovog antiaritmijskog efekta.", publisher = "Pharmaceutical Association of Serbia", journal = "Arhiv za farmaciju", title = "Antiarrhythmic effects of newly developed propafenone derivatives, Antiaritmički efekti novosintetisanih derivata propafenona", volume = "72", number = "4", pages = "392-412", doi = "10.5937/arhfarm72-37114" }
Ivković, B., Opačić, D., Džudović, B., Crevar, M.,& Gojković-Bukarica, L.. (2022). Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju Pharmaceutical Association of Serbia., 72(4), 392-412. https://doi.org/10.5937/arhfarm72-37114
Ivković B, Opačić D, Džudović B, Crevar M, Gojković-Bukarica L. Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju. 2022;72(4):392-412. doi:10.5937/arhfarm72-37114 .
Ivković, Branka, Opačić, Dragan, Džudović, Boris, Crevar, Milkica, Gojković-Bukarica, Ljiljana, "Antiarrhythmic effects of newly developed propafenone derivatives" in Arhiv za farmaciju, 72, no. 4 (2022):392-412, https://doi.org/10.5937/arhfarm72-37114 . .