Biological Activity
am 92016 hydrochloride is a specific inhibitor of delayed rectifier potassium current [1].potassium channel is an ion channel and acts to reset the resting potential and shapes the action potential. delayed rectifier potassium channel (ik) is activated by the influx of na+ and discharges k+, which repolarizes the membrane. ik restricts the duration of the nerve impulse.am 92016 hydrochloride is a specific ik inhibitor. in guinea-pig and rabbit ventricular cells, am 92016 significantly increased action potential duration with 20% and 90% repolarization levels, respectively. also, am 92016 (1 μm) inhibited ik activated by step depolarizations in a time-dependent way [1]. in rabbit sino-atrial node cells, am 92016 (50 nm) significantly inhibited ik with ic50 value of 40 nm in a concentration-dependent way [2]. in vascular smooth muscle cells (vsmc), am92016 hydrochloride inhibited no-induced erk1/2 dephosphorylation [3].in guinea-pigs, am 92016 (1-5 mg/kg) significantly increased heart rate, left ventricular systolic pressure, systolic arterial blood pressure and the contractile index dp dtmax. am 92016 exhibited proarrhythmic activity [4].
References
[1]. connors sp, gill ew, terrar da. actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells. br j pharmacol, 1992, 106(4): 958-965.
[2]. lei m, brown hf. inhibition by compound ii, a sotalol analogue, of delayed rectifier current (ik) in rabbit isolated sino-atrial node cells. naunyn schmiedebergs arch pharmacol, 1998, 357(3): 260-267.
[3]. palen di, belmadani s, lucchesi pa, et al. role of shp-1, kv.1.2, and cgmp in nitric oxide-induced erk1/2 map kinase dephosphorylation in rat vascular smooth muscle cells. cardiovasc res, 2005, 68(2): 268-277.
[4]. hagerty mj, wainwright cl, kane ka. the in-vivo cardiovascular effects of a putative class iii anti-arrhythmic drug, am 92016. j pharm pharmacol, 1996, 48(4): 417-421.
