In vivo metoclopramide protection of cholinesterase from paraoxon inhibition: direct comparison with pralidoxime in subchronic low-dose exposure

✍ Scribed by M. Y. Hasan; S. M. Nurulain; K. Arafat; O. P. Naseer; G. A. Petroianu

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 94 KB
• Volume: 24
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.980

✦ Synopsis

Abstract

The benzamide compound metoclopramide (MCP) protects against cholinesterase inhibition by paraoxon (POX) both in vitro and in vivo. This study evaluates MCP‐conferred protection of enzyme activity head to head against the therapeutic gold standard pralidoxime (PRX). Six groups of rats were used. All substances were applied i.p. daily for 5 days, followed by a 2‐day rest. The 7‐day cycle was repeated eight times. Group 1 received 100 nM POX, group 2 received 50 µM MCP, group 3 received 100 nM POX + 50 µM MCP, group 4 received 50 µM PRX, group 5 received 100 nM POX + 50 µM PRX and group 6 received saline. Red blood cell acetylcholinesterase (RBC‐AChE) measurements were performed at baseline and on day 5 of each 7‐day cycle. The sums of enzyme activities over time (weekly values expressed as % of baseline of 100%) were compared using the Mann–Whitney rank order test. A Bonferroni correction of 4 for multiple comparisons was applied. Paraoxon significantly reduced enzyme activities when compared with saline (Σ = 535 ± 25 vs 902 ± 42). Metoclopramide conferred statistically significant in vivo protection from inhibition of RBC‐AChE by POX (Σ = 640 ± 58). The extent of protection was significantly less than that conferred by the gold standard PRX (Σ = 765 ± 57). Metoclopramide, in addition to being less effective as an RBC‐AChE protective agent, also caused a failure to thrive in the POX+MCP‐exposed rats, as evidenced by the changes in body weight. Copyright © 2004 John Wiley & Sons, Ltd.