Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels

European Journal of Pharmacology
M K Pugsley, A L Goldin

Abstract

The effects of bisaramil, a novel diazabicyclononane antiarrhythmic agent, were compared to those of lidocaine, a clinically used class Ib antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels expressed in Xenopus laevis oocytes using a two-electrode voltage clamp. Both bisaramil and lidocaine produced a concentration-dependent tonic block of Na+ current that was most effective on cardiac channels, but bisaramil was more potent than lidocaine. Both drugs produced a concentration-dependent shift in the voltage-dependence of inactivation and delayed recovery from inactivation. Bisaramil produced marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle and brain channels, whereas lidocaine produced marked frequency-dependent block of all three channel types. Therefore, bisaramil shows tonic and frequency-dependent blockade that is most potent against the heart Na+ channel, which may account for its potent antiarrhythmic efficacy in vivo, and may result in reduced central nervous system toxicity compared to clinically used agents such as lidocaine.

References

Oct 1, 1976·Anesthesiology·G Strichartz
Nov 14, 1977·Biochimica Et Biophysica Acta·L M Hondeghem, B G Katzung
Apr 22, 1992·European Journal of Pharmacology·J NittaM Hiraoka
Nov 1, 1992·European Heart Journal·M J Janse
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·V J AuldR J Dunn
Jul 1, 1990·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·M ParóczaiF Solti
Aug 1, 1987·Naunyn-Schmiedeberg's Archives of Pharmacology·T MatsubaraL Hondeghem
Dec 1, 1988·Journal of Molecular and Cellular Cardiology·C W ClarksonL M Hondeghem
Apr 1, 1984·Journal of Clinical Pharmacology·E M Vaughan Williams
May 1, 1983·Circulation Research·J Sanchez-ChapulaI R Josephson
May 1, 1983·The Journal of General Physiology·B P BeanR W Tsien
Jan 1, 1995·British Journal of Pharmacology·M K Pugsley, D A Saint
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·Y QuW A Catterall
Apr 1, 1996·Biophysical Journal·D W WangP B Bennett
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·D S RagsdaleW A Catterall
Sep 1, 1996·Japanese Heart Journal·J C Makielski

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Citations

Apr 7, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Paul W LenkowskiManoj K Patel
Jun 16, 1999·British Journal of Pharmacology·M K Pugsley, A L Goldin
Jul 25, 2000·British Journal of Pharmacology·G HaeselerM Leuwer
Oct 5, 2010·Insect Biochemistry and Molecular Biology·Weizhong SongKe Dong
Oct 7, 2004·Biophysical Journal·W Zhou, A L Goldin
Mar 10, 2007·European Journal of Pharmacology·Jun-Ho LeeSeung-Yeol Nah
Mar 26, 2003·European Journal of Anaesthesiology·M SchywalskyH Schwilden
Mar 26, 2003·European Journal of Anaesthesiology·P BozkurtM Hacibekiroğlu
Mar 26, 2003·European Journal of Anaesthesiology·T P WeberM Booke
Mar 26, 2003·European Journal of Anaesthesiology·S G Sakka, A Meier-Hellmann
Mar 26, 2003·European Journal of Anaesthesiology·J A BlunkW Koppert
Mar 26, 2003·European Journal of Anaesthesiology·P KrankeN Roewer
Dec 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·M K PugsleyM J A Walker
Sep 14, 2004·Journal of Combinatorial Chemistry·Alexander V IvachtchenkoAlexander V Khvat
Jun 1, 2010·Pesticide Biochemistry and Physiology·Kristopher S SilverKe Dong

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