Phenothiazines inhibit acetylcholinesterase by concentration-dependent-type kinetics. A study with trifluoperazine and perphenazine.
The properties of perphenazine (PPZ) and trifluoperazine (TFP) as fluorescent dyes were exploited to calculate their critical micellar concentrations. The relative fluorescence quantum yield of the two amphiphiles was dependent on their concentration, abruptly decreasing above 30-40 microM PPZ and 20-30 microM TFP. Evidence is presented that this phenomenon is driven by the formation of non-fluorescent drug aggregates. The type of inhibition kinetics displayed by PPZ and TFP on human erythrocyte acetylcholinesterase (AChE) was also dependent on drug concentration, turning from non-competitive to a "mixed" inhibition type at concentrations at which PPZ and TFP were demonstrated to undergo micelle formation. Results support the notion that phenothiazines may interact with AChE both as monomers and micellar aggregates, producing different inhibitory effects.
Spinedi
A
A
Department of Biology, University of Rome Tor Vergata, Italy.
Pacini
L
L
Limatola
C
C
Luly
P
P
Farias
R N
RN
D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005456:Fluorescent Dyes; D006801:Humans; D007700:Kinetics; D010546:Perphenazine / Q000494:pharmacology*; D013696:Temperature; D014268:Trifluoperazine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D005456:Fluorescent Dyes; D014268:Trifluoperazine; D000110:Acetylcholinesterase; D010546:Perphenazine