文摘
Inhibitory effects of the dopamine D2-receptor antagonistic benzamide compound metoclopramide (MCP) on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and human caudate nucleus and on human serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric assay with acetylthiocholine (ASCh) as substrate. MCP concentrations in the assays varied from 0.30μMto 0.15mM. All isoenzymes studied were inhibited by metoclopramide in a concentration-dependent manner. MCP inhibition of AChE and ChE isoenzymes was not time-dependent and of the reversible type. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that, for AChE isoenzymes of erythrocytes and of the caudate nucleus, MCP reduced both maximal reaction velocity (Vmax) and substrate affinity (apparent Michaelis constant,KM, increased). Thus, MCP inhibition of both AChE isoenzymes was of mixed competitive/non-competitive type. MCP constants for reversible competitive (Ki) and non-competitive (Ki′) inhibition could be determined for erythrocyte AChE (Ki