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Topiramate as an Inhibitor of Carbonic Anhydrase Isoenzymes
Author(s) -
Dodgson Susanna J.,
Shank Richard P.,
Maryanoff Bruce E.
Publication year - 2000
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.2000.tb02169.x
Subject(s) - carbonic anhydrase , topiramate , chemistry , acetazolamide , isozyme , carbonic anhydrase inhibitor , carbonic anhydrase i , enzyme , biochemistry , medicine , epilepsy , psychiatry
Summary: Purpose : This study investigated the effectiveness of topiramate (TPM) as an inhibitor of six isozymes of carbonic anhydrase (CA). Methods : The inhibition constants (K i ) of TPM and acetazolamide (AZM) for CA I, CA II, CA III, CA IV, CA V, and CA VI were determined for human (HCA), rat (RCA), or mouse (MCA). The activity of CA was studied by using purified isozymes, erythrocytes, subcellular fractions of kidney or brain, and saliva, and was assayed at 37°C or 25°C by 18 O mass spectrometry and/or by measuring the pH shift at 0°C. Results : Topiramate K i values for HCA I, HCA II, HCA IV, and HCA VI were ∼100, 7, 10, and >100 μ M , respectively. TPM K i values for RCA I, RCA II, RCA III, RCA IV, and RCA V were ∼180, 0·1 to 1, >100, 0·2 to 10 and 18 μ M , respectively. For RCA II and RCA IV, the K i values were temperature dependent. TPM K i values for MCA II and MCA IV ranged between 1 and 20 μ M . Conclusions : These results indicate that TPM is more potent as an inhibitor of CA II and CA IV than of CA I, CA III, and CA VI. In all three species, AZM was usually 10 to 100 times more potent than TPM as an inhibitor of CA isozymes.