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 Ca(2+) channels. Here, whole-cell Ca(2+) 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 IC(50) 10 and 56 microM, respectively. A therapeutic concentration of lamotrigine (10 microM) 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 microM).
Hainsworth
Atticus H
AH
Pharmacology Research Group, School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK.
McNaughton
Nicolle C L
NC
Pereverzev
Alexey
A
Schneider
Toni
T
Randall
Andrew D
AD
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020908:Calcium Channels, R-Type / Q000187:drug effects* / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000502:physiology; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D006801:Humans; D000077213:Lamotrigine; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology*
C443646:2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine; C423009:CACNA1E protein, human; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D020747:Calcium Channels, T-Type; D027682:Cation Transport Proteins; D010879:Piperazines; D011743:Pyrimidines; D014227:Triazines; C081980:sipatrigine; D000077213:Lamotrigine