Actions of sipatrigine, 202W92 and lamotrigine on R-type and T-type Ca2+ channel currents

Relatively little has been published on the pharmacology of R-type and T-type Ca2+ channels. Here, whole-cell Ca2+ channel currents were recorded from human embryonic kidney 293 cell-lines transfected with either alpha1E subunits (R-type currents) or alpha1G or alpha1I subunits (T-type currents). R-type currents were inhibited by sipatrigine and the related compound 202W92 (R-(-)-2,4-diamino-6-(fluromethyl)-5(2,3,5-trichlorophenyl)pyrimidine) with IC50 10 and 56 muM, respectively. A therapeutic concentration of lamotrigine (10 muM) inhibited R-type currents (30%) but was without effect on alpha1I-mediated T-type currents. Lamotrigine was also a weak inhibitor of T-type currents mediated by alpha1G subunits (< 10% inhibition by 100 muM). (C) 2003 Elsevier Science B.V. All rights reserved.