Protein ligand interactions. Part 5: Isoquinoline alkaloids as inhibitors of acetylcholinesterase from Electrophorus electricus

Abstract

Kinetic analysis has shown that papaverine, berberine and isoquinoline alkaloids acts as reversible competitive inhibitors of acetylcholinesterase with respect to the substrate, acetylthiocholine chloride. The inhibitor constants (Ki) vary from 3.5 microM to 88 microM. With time they act as irreversible covalent inhibitors with papaverine producing 85% inactivation after 40 min. Pseudo first-order kinetics are observed with the rate constant being proportional to the concentration of the ligand and the order of reaction being equal to one. Spectrophotometry was used to study the binding of the ligands with acetylcholinesterase and Scatchard analysis used to calculate the respective dissociation constants and the number of binding sites.