Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity.
This study examines the effect of the antidepressants fluoxetine, sertraline and amitriptyline on cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) activities in human serum and erythrocyte membrane (ghost). The concentrations used range from 3 to 60 microM for fluoxetine and amitriptyline and 0.3 to 12 microM for sertraline. At the micromolar range concentration, different classes of antidepressants, including fluoxetine and sertraline (selective serotonin reuptake inhibitors (SSRIs)) and amitriptyline (tricyclic antidepressant) inhibited human serum cholinesterase. The order of inhibitory potency was sertraline>amitriptyline>>fluoxetine and the IC(50) values were 4.05, 9.43 and 62 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants was mixed in nature. At the micromolar range concentration, sertraline (60-120 microM) and amitriptyline (60-180 microM) inhibited human erythrocyte AChE. The order of inhibitory potency was sertraline>amitriptyline and the IC(50) values were 80 and 134 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants in AChE human erythrocyte membrane (ghost) was mixed in nature. The interaction of sertraline with the cholinesterase is labile since the removal of inhibitor by gel filtration recovered completely the enzyme activity. Our results demonstrate that the usual clinical antidepressants are inhibitors of the cholinesterases on human serum and erythrocyte membrane.
Müller
Tatiane C
TC
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, RS, Brazil.
Rocha
João Batista T
JB
Morsch
Vera M
VM
Neis
Roseli Tatto
RT
Schetinger
Maria R C
MR
D000110:Acetylcholinesterase / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000097:blood*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology
D000110:Acetylcholinesterase; D000639:Amitriptyline; D000928:Antidepressive Agents; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline