Preclinical study comparing the antidotal effect of clonidine with atropine for the treatment of acute malathion poisoning in the albino rats

Suresha K. R., SantoshKumar M., . Nagashayana


Background: In developing countries 2–3 million people are acutely poisoned by organophosphorus (OP) pesticides every year. There is a pressing need for new affordable antidotes and in this context clonidine which has central effect (α2 agonist) has been evaluated in the albino rats presenting with signs or symptoms of acute malathion poisoning. And compared with atropine for the acte malathion poisoning in albino rats.

Methods: This was a preclinical study conducted on albino rats of either sex weighing 100-150 grams were randomly divided into 4 groups (6/group). Malathion was given at the lethal dose of 54 mg/kg body weight (BW) by gavage to each group. Group 1: normal saline intraperioneal (i.p). Group 2: Post treated with atropine 1.5 mg/kg BW (i.p). Group 3: Pre treated with clonidine 1mg/ kg BW (i.p), 10 minutes priore malathion. Group 4: Pre treated with clonidine and post treated with atropine. The above groups were observed for straub tail, muscle fasciculation, piloerection, lacrimation, defecation/ urination; salivation, tremors, gasping and convulsion and were recorded at time 0, 15, 30, 45 and 60 minutes after poisoning. The latency of onset of tremors, loss of righting reflex and tremors were recorded. Results were presented as percentage occurrence and Mean ± SEM. Repeated measure one way ANOVA and Fisher’s Least Significant Difference post hoc test for comparison between groups. P-value of 0.05 or less was considered for statistical significance.

Results: The central effects namely straubs tail and whole body tremors are significantly improved compared to control and atropine with clonidine group (p<0.05). However convulsion shows improve in atropine alone and atropine with clonidine groups. The overall survival time has significantly increased compared to control and atropine and atropine with clonidine (P<0.05).Clonidine has not shown any effect on survival time.

Conclusions: Clonidine has some central protective effect in malathion poisoning. And it has not shown any effect on survival time. This issue needs further controlled studies.


Atropine, Clonidine, Malathion, Organophosphate

Full Text:



Al-Othman AM, Al-Numair KS, El-Desoky GE, Al Othman KYZA, Aboul-Soud MAM. Protection of α-tocopherol and selenium against acute effects of malathion on liver and kidney of rats. Afr J Pharm Pharmacol. 2011;5(10):1263-71.

Gunnell D, Eddleston M, Phillips MR, Konradsen F. BMC Public Health. 2007;21(7):1-15.

KoeHe GB. Pharmacoogy and Toxicology of Organophosphates. In: Ballanty Be and Marre TC eds.Clinical and Experimental Toxicology of Organophosphates and Carbamates. Oxford: Butterworthl Heiman; 1992:40-46.

Zhou Z, Hu Y, Sun Y, Chen J. Protective Effect of Clonidine against toxicity of Organophosphorus Pesticides. J Occup Health. 200l;43:346-50.

Clinico-Epidemiological Characteristics of Patients Presenting with Organophosphorus Poisoning. Indranil Banerjee, SK Tripathi, and A Sinha Roy. N Am J Med Sci. 2012;4(3):147-50.

Balali-Mood M, Saber H. Recent Advances in the Treatment of Organophosphorous Poisonings. Iran J Med Sci. 2012;37(2):74-91.

Nurulain SM. Different approaches to acute organophosphorus poison treatment. J Pak Med Assoc. 2012;62(7):712-5.

Ramakrishnan K, Ramesh K, Sathyajith NG. Role of clonidine in organophosphate poisoning in children. J Indian Soc Toxicol. 2005;1:30-1.

Polwattage MSP, Jayamanna SF, Hettiarachchi R, Abeysinghe C, Karunatilake H, Dawson AH. A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning. Trials. 2009;10:73.

Magri V, Buccafusco JJ, Aronstam RS. Protection by clonidine from cardiovascular changes and lethality following soman administration in the rat: role of brain acetylcholine. Toxicol Appl Pharmacol. 1988;95:464-73.

Mohammad FK, Gada AMF, Shindala MK. Comparative antidotal effects of diphenhydramine and atropine against dichlorvos-induced acute toxicosis in rats. Vet archive. 2002;72(1):19-28.

Holy B, Oruambo F, Kenanagha B. Poor antedotal effects of copper and manganese on rats expossed to acute dose of dichlorvos. Ejpmr. 2015;2(1):290-303.

Yurumez Y, Durukan P, Yavuz Y. Acute organophosphate poisoning in university hospital emergency room patients. Internal Medicine. 2007;46(13):965-9.

Chedi BAZ, Aliyu M. Effect and management of dichlorvos poisoning in Wistar rats. Bayero Journal of Pure and Applied Sciences. 2010;3(2):1-3.

Buccafusco JJ, Aronstam RS. Clonidine protection from the toxicity of soman, an organophosphate acetylcholine esteraseinhibitor, in the mouse. J Pharmacol Exp Ther. 1986;239:43-6.

Liu WF. A symptomatological assessment of organophosphate-induced lethality in mice: Comparison of atropine and clonidine protection. Toxicol Lett. 1991;56:19-32.