Guanfu base A is an antiarrhythmic alkaloid isolated from Aconitum coreanum and is a potent noncompetitive CYP2D6 inhibitor, with a K_i of 1.20 μM in human liver microsomes (HLMs) and a K_i of 0.37 μM for the human recombinant form (rCYP2D6). Guanfu base A is also a potent competitive inhibitor of CYP2D in monkey (K_i of 0.38 μM) and dog (K_i of 2.4 μM) microsomes^[1]. Guanfu base A also inhibits HERG channel current^[2]. IC50 & Target: CYP2D6^[1]; HERG channel^[2] In Vitro: Guanfu base A has no inhibitory activity on mouse or rat CYP2Ds. Guanfu base A does not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but shows slight inhibition of 2B6 and 2E1^[1].
Guanfu base A is a potent inhibitor of CYP2D6, with an IC₅₀ recorded at ~0.46 μM in HLM (Dextromethorphan 5 μM) and 0.12 μM in rCYP2D6 (Bufuralol 5 μM)^[1].
The effects of Guanfu base A is investigated in human embryonic kidney 293 (HEK293) cells transiently transfected with HERG complementary DNA using a whole-cell patch clamp technique. Guanfu base A inhibits HERG channel current in concentration-, voltage-, and time-dependent manners with an IC₅₀ of 1.64 mM. Guanfu base A shifts the activation curve in a negative direction and accelerated channel inactivation but shows no effect on the inactivation curve^[2]. In Vivo: Beagle dogs treated intravenously with Dextromethorphan (2 mg/mL) after pretreatment with Guanfu base A injection shows reduced CYP2D metabolic activity, with the C_max of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration-time curve half that of the saline-treated group^[1].