New Drug Hydrochloride Off With A Prime Anti-arrhythmic Effects Of Experimental And Clinical Studies

Hydrochloric Guanfu base A (GFA) is a new anti-arrhythmic alkaloid with a structure of C20-diterpenoid isolated from the tuber of Aconitum coreanum (Levl.) Raipaics in China. In pre-clinical studies it was shown to slow conduction velocity in nearly all compartments of the heart in vivo and in vitro and exhibited anti-arrhythmic effects in various experimental arrhythmia animal models.Effects of hydrochloric guanfu base A on heart L-type calcium current in rat ventricular myocytesOBJECTIVE: The effects of guanfu base A on L-type calcium current (ICa-L) were evaluated under whole-cell recording condition in isolated rat ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. ICa-L was elicited by depolarization from a holding potential of -50 mV using whole-cell recording techniques.RESULTS: 1. 25,125,250, 1000μM GFA produced a concentration-dependent reduction of peak L-type calcium current [ ICa-L (pA/pF), at 0mV ] to 81.76%,77.54%, 76.46%, 64.77% from control (P<0.05). 2.GFA upshifted the current-voltage relation (I-V) curves, but the activation voltage, the maximal activation voltage were not significantly altered by GFA. 3.GFA blocked ICa-L in a mild use-dependent manner and GFA exerted a tonic block, which may result from drug interaction with the resting state of the channel. 4. The steady-state activation curve of ICa-L was not significantly affected. 5.GFA significantly delayed the time constant ( τ ) of recovery of ICa-L from inactivation which may suggest that the drug interact with the inactive state of the channel in addition to with resting state.CONCLUSION: 1.A relatively moderate inhibition of GFA on ICa-L was found, which may not be the principal mechanism of its anti-arrhythmic effect. 2.GFA acts on the resting state and may on the inactivated state of L-type calcium channel.