title: Effects of AN-132, a novel antiarrhythmic lidocaine analogue, and of lidocaine on membrane ionic currents of guinea-pig ventricular myocytes.
abstract: We studied the effects of AN-132 (10, 30 and 100 mumol/l), an analogue of lidocaine, on membrane currents and action potentials of single guinea-pig ventricular cells using whole-cell clamp techniques. The effects of lidocaine, an authentic class I antiarrhythmic agent were used for comparative purposes. (1) AN-132 decreased the Na current (INa) in a concentration-dependent manner, with a greater efficacy than seen with lidocaine. The concentration of the half maximal inhibition on INa (Kd) was 31.7 mumol/l for AN-132 and 94.9 mumol/l for lidocaine. (2) AN-132 also decreased the Ca current (ICa), concentration-dependently, while lidocaine had only a minor effect on ICa. The half maximal inhibition on ICa (Kd) was 23.1 mumol/l and 27.4 mumol/l for AN-132 and lidocaine, respectively. (3) AN-132 decreased the IK1, in a concentration-dependent manner; lidocaine was without effect. (4) AN-132 increased the unspecified steady state outward current, at positive potentials and depressed the time- and voltage-dependent outward K current (IK). Lidocaine had no effect on either current. (5) AN-132 shortened the action potential duration (APD), in a concentration-dependent manner, without altering the resting potential. From these findings, we conclude that apart from a potent inhibitory effect on INa, AN-132 had a variety of effects on other currents, properties not shared by lidocaine. Such multiple blocking effects on the membrane currents may relate to the alleged potent antiarrhythmic effect of AN-132.
authors: Department of Physiology, Medical College of Oita, Japan.
authors: K
authors: K
authors: Ono
authors: T
authors: T
authors: Kiyosue
authors: M
authors: M
authors: Arita
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D005029:Ethylenediamines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: C053205:3-(diisopropylaminoethylamino)-2',6'-dimethylpropionanilide, diphosphoric acid; D000813:Anilides; D000889:Anti-Arrhythmia Agents; D005029:Ethylenediamines; D007473:Ion Channels; D015222:Sodium Channels; D008012:Lidocaine