Comparative study of the inhibitory effect of antidepressants on cholinesterase activity in Bungarus sindanus (krait) venom, human serum and rat striatum.
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 IC(50) 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.
Ahmed
Mushtaq
M
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Brazil.
Batista
João
J
Rocha
T
T
Mazzanti
Cinthia M
CM
Hassan
Waseem
W
Morsch
Vera M
VM
Loro
Vânia Lúcia
VL
Thomé
Gustavo
G
Schetinger
Maria R C
MR
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D017838:Bungarus / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D017072:Neostriatum / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases