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Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of isozymes I and II.

Abstract：

:The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citalopram have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: histamine and phenylalanine. All three SSRI activated both isozymes with potencies comparable to that of the standards although the profile was different: for hCA I, best activators were fluoxetine and histamine, with citalopram and sertraline showing weaker activity. For hCA II, the best activators were phenylalanine and citalopram, and the weakest histamine and sertraline, whereas fluoxetine showed an intermediate behavior. These results suggest that SSRI efficacy in major depression complicating Alzheimer's disease may be partly due to their ability to activate CA isozymes and may lead to the development of potent activators for the therapy of diseases associated with significant decreases in brain CA activity.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Casini A,Caccia S,Scozzafava A,Supuran CT

doi

10.1016/s0960-894x(03)00507-9

subject

Has Abstract

pub_date

2003-08-18 00:00:00

pages

2765-8

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960894X03005079

journal_volume

13

pub_type

杂志文章

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