In vitro and in vivo effects of dantrolene on carbonic anhydrase enzyme activities

Abstract

The effects of dantrolene were investigated on carbonic anhydrase (CA) enzyme activities in in vitro human and in in vivo Sprague-Dawley rat erythrocytes. For in vitro study, human carbonic anhydrase-I (HCA-I) and -II (HCA-II) were purified by Sepharose 4B-L-tyrosine-sulfanylamide affinity chromatography, rats were used for in vivo study. In vivo and in vitro CA enzyme activity was determined colorimetrically using the CO2-hydration method of Wilbur and Anderson. Dantrolene (1.64×10-5-6. 56×10-5M) showed in vitro inhibitory effects on HCA-I and HCA-II hydratase activity, when determined using the CO2-hydratase method. 50% inhibitory concentration (IC50) was 4.09×10 -5M for HCA-I and 3.24×10-5M for HCA-II. Rat erythrocyte CA activity was significantly inhibited by 10 mg/kg dantrolene for up to 3 h (p<0.001) following intraperitoneal administration. In conclusion, Dantrolene inhibited the carbonic anhydrase enzyme activity under in vitro and in vivo conditions. © 2004 Pharmaceutical Society of Japan.