Protective drugs in acute large-dose exposure to organophosphates: A comparison of metoclopramide and tiapride with pralidoxime in rats

Georg A. Petroianu, Mohammed Y. Hasan, Syed M. Nurulain, Kholoud Arafat, Rajan Sheen, Ayman Saleh, Andrea Schmitt

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Weak and reversible inhibitors of cholinesterase(s), when coadministered in excess with a more potent inhibitor such as organophosphates, can act in a protective manner. The benzamide compound, metoclopramide, confers some protection (putatively via this mechanism) for cholinesterases against inhibition by paraoxon both in vitro and in vivo, after chronic small-dose exposure. Tiapride is a related benzamide. In this study, we compared the protection by metoclopramide and tiapride in rats acutely exposed to large doses of paraoxon with the therapeutic " gold standard," pralidoxime. Group 1 received 1 μmol paraoxon (approximately 75% lethal dose), Group 2 received 50 μmol metoclopramide, Group 3 received 50 μmol tiapride, Group 4 received 50 μmol pralidoxime, Group 5 received 1 μmol paraoxon + 50 μmol metoclopramide, Group 6 1 μmol paraoxon + 50 μmol tiapride, and Group 7 1 μ paraoxon + 50 μmol pralidoxime. All substances were administered intraperitoneally. The animals were monitored for 48 h and mortality was recorded at 30 min, 1,2,3,4,24, and 48 h. Blood was taken for red blood cell acetylcholinesterase measurements at baseline, 30 min, 24, and 48 h. With the exception of Group 7, in which some late mortality was observed, mortality occurred mainly in the first 30 min after paraoxon administration with minimal changes occurring thereafter. Mortality at 30 min was 0% in the metoclopramide, tiapride, and pralidoxime groups and 73 ± 20 (paraoxon), 65 ± 15 (paraoxon + metoclopramide), 38 ± 14 (paraoxon + tiapride), and 13 ± 19 (paraoxon + pralidoxime). Mortality at 48 h was 75 ± 18 (paraoxon), 67 ± 17 (paraoxon + metoclopramide), 42 ± 16 (paraoxon + tiapride), and 27 ±24 (paraoxon + pralidoxime). Metoclopramide does not significantly influence mortality after acute large-dose paraoxon exposure. Both tiapride and pralidoxime significantly decreased mortality in our model. The protection conferred by tiapride was significantly less than that conferred by pralidoxime at 30 min, but was not significantly different at 24 and 48 h.

Original languageEnglish
Pages (from-to)382-386
Number of pages5
JournalAnesthesia and Analgesia
Volume100
Issue number2
DOIs
Publication statusPublished - Feb 2005

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Fingerprint

Dive into the research topics of 'Protective drugs in acute large-dose exposure to organophosphates: A comparison of metoclopramide and tiapride with pralidoxime in rats'. Together they form a unique fingerprint.

Cite this