Zantac Research Today is a free monthly online journal that collates and summarizes the latest research about Zantac, including details on ranitidine, side-effects, allergic reactions, information. | ||||||||
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Ranitidine in acute high-dose organophosphate exposure in rats: effect of the time-point of administration and comparison with pyridostigmine.Petroianu GA, Hasan MY, Nurulain SM, Shafiullah M, Sheen R, Nagelkerke N Department of Pharmacology & Therapeutics, Faculty of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates. Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H(2)) receptor blocker ranitidine is among H(2) blockers the most potent inhibitor of acetylcholinesterase but roughly three to four orders of magnitude less potent than paraoxon (an irreversible organophosphate esterase inhibitor) or pyridostigmine (a reversible carbamate esterase inhibitor). We have previously shown that in vitro ranitidine confers some protection against inhibition of cholinesterases by paraoxon and that in vivo it both increases the number of rats surviving an acute paraoxon exposure and also protects to some degree the cholinesterases from organophosphate inhibition. The purpose of the study was to compare in a prospective non-blinded study, in a rat model of acute high-dose paraoxon exposure, ranitidine with pyridostigmine either administered simultaneously or 30 min. before exposure. There were 36 rats in each of the 5 groups. All substances were applied intraperitoneally. Additional analysis included data from a similar experiment carried out in 2005, in which 54 rats were exposed to paraoxon only (G(1)) and 54 to paraoxon+ranitidine simultaneously (G(2)). All groups (except controls; G(6) & G(7)) received 1 muMol paraoxon ( approximately LD(75)); groups 2-5 received in addition to paraoxon: G(2): 50 muMol ranitidine within 1 min. of paraoxon, G(3): 1 muMol pyridostigmine within 1 min. of paraoxon, G(4): 50 muMol ranitidine 30 min. before paraoxon, G(5): 1 muMol pyridostigmine 30 min. before paraoxon. Groups 6 & 7 received only ranitidine and pyridostigmine respectively, group G(1) received only paraoxon. Mortality was recorded at 30 min., 1, 2, 3, 4, 24 and 48 hr. Mortality data were compared using Kaplan-Meier plots and logrank tests. No Bonferroni correction for multiple comparisons was applied and an alpha</=0.05 was considered significant. All statistical analysis was performed by using SPSS 12.0 statistical software (SPSS Inc., Chicago, IL, USA). Simultaneous administration of ranitidine or pyridostigmine with paraoxon does not significantly affect mortality. Pretreatment (30 min. before) with both ranitidine or pyridostigmine statistically and significantly reduced mortality. When administered before paraoxon, pyridostigmine is statistically significantly superior to ranitidine. Both ranitidine and pyridostigmine are protective against acute paraoxon toxicity provided they are administered before paraoxon. Pyridostigmine results are statistically significantly superior to ranitidine (</=0.05). Published 16 October 2006 in Basic Clin Pharmacol Toxicol, 99(4): 312-6.
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