Kufotokozera

LCZ696 (Sacubitril/Valsartan), yopangidwa ndi Valsartan (an ARB) ndi Sacubitril (AHU377) mu 1: 1 molar ratio, ndi yoyamba mu kalasi, pakamwa bioavailable, ndi awiri-acting angiotensin receptor-neprilysin (ARN) inhibitor kwa hypertension. ndi kulephera kwa mtima [1] [2] [3].LCZ696 imathandizira matenda a shuga a cardiomyopathy poletsa kutupa, kupsinjika kwa okosijeni ndi apoptosis.

Mbiri

LCZ696 ndi yoyamba m'kalasi ya ARNi (angiotensin receptor neprilysin inhibitor) yomwe imakhala ndi anionic moieties ya AR valsartan ndi neprilysin inhibitor prodrug AHU377 (1: 1 chiŵerengero) cha kulephera kwa mtima ndi matenda oopsa.

Ma angiotensin receptors ndi ma G-protein-coupled receptors.Amayimira pakati pamtima ndi zotsatira zina za angiotensin II yomwe ndi bioactive peptide ya renin-angiotensin system.Neprilysin ndi endopeptidase yopanda ndale yomwe imawononga ma peptides amkati a vasoactive monga natriuretic peptides.Kuletsa kwa neprilysin kumawonjezera kuchuluka kwa ma peptides a natriuretic omwe amathandizira pakuteteza mtima, mitsempha ndi aimpso.[1]

Mu makoswe a Sprague-Dawley, kuwongolera pakamwa kwa LCZ696 kunapangitsa kuti pakhale kukwera kodalira kwa mlingo wa immunoreactivity wa peptide ya atrial natriuretic chifukwa cha kuletsa kwa neprilysin.Mu makoswe amtundu wapawiri wa transgenic, LCZ696 idapangitsa kudalira kwa mlingo komanso kuchepetsedwa kosalekeza kwa kupanikizika kwapakati.Ophunzira athanzi, kafukufuku wopangidwa mwachisawawa, wakhungu kawiri, woyendetsedwa ndi placebo adatsimikizira kuti LCZ696 idapereka inhibition ya neprilysin inhibition ndi AT1 receptor blockade.LCZ696 inali yotetezeka komanso yololera mwa anthu.[2] [3]

Zolozera:
McMurray JJ, Packer M, Desai AS et al.Angiotensin-neprilysin inhibition motsutsana ndi enalapril mu kulephera kwa mtima.N Engl J Med.2014 Sep 11; 371(11): 993-1004.
Gu J, Noe A, Chandra P, Al-Fayoumi S et al.Pharmacokinetics ndi pharmacodynamics ya LCZ696, novel-acting angiotensin receptor-neprilysin inhibitor (ARNi).J Clin Pharmacol.2010 Apr;50(4):401-14.
Langenickel TH, Dole WP.Angiotensin receptor-neprilysin inhibition ndi LCZ696: njira yatsopano yochizira kulephera kwa mtima, Drug Discov Today: Ther Strategies (2014),

Kusungirako

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