Comparative study of the inhibitory effect of antidepressants on cholinesterase activity in Bungarus sindanus (krait) venom, human serum and rat striatum

Abstract

Cholinesterases are divided into two classes based on differences in their substrate specificity and tissue distribution: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes may be inhibited by several compounds, such as antidepressants. The antidepressants paroxetine, imipramine, clomipramine and sertraline inhibited both venom AChE as well as human serum BChE in a concentration-dependent manner but had no effect on AChE in the rat brain striatum. The IC₅₀ of venom calculated for imipramine was 0.3 mM, paroxetine 0.38 mM, clomipramine 0.34 mM and sertraline 0.35 mM. Analysis of kinetic data indicated that the inhibition caused by sertraline and paroxetine was mixed, i.e. K_m values increased and V_max decreased in a concentration dependent manner. Imipramine and clomipramine exhibited competitive inhibition, i.e. K_m values increased and V_max remained constant. The present results suggest that these therapeutic agents used for depression can also be considered as inhibitors of snake venom and human serum cholinesterase.

Keywords::

• Antidepressant
• cholinesterase
• snake venom
• human serum
• rat striatum, inhibitors

Acknowledgements

We wish to thank the Academy of Sciences for the Developing World (TWAS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for the fellowship awarded to Mushtaq Ahmed (TWAS-CNPq/Brazil-Pakistan), and FINEP research grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)” # 01.06.0842-00.