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Efficacy of an adenosine A1 receptor agonist compared with atropine and pralidoxime in a rat model of organophosphate poisoning

Department of Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey

B U Ergur

Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Izmir, Turkey

A Akgun

Department of Pharmacology, Dokuz Eylul University Health Sciences Institute, Izmir, Turkey

Y C Kaplan

Department of Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey

A O Kinay

Deparment of Statistics, Faculty of Arts and Sciences, Dokuz Eylul University, Izmir, Turkey

Y Tuncok

Department of Pharmacology, School of Medicine, Dokuz Eylul University, Balcova, 35340 Izmir, Turkey; yesim.tuncok{at}deu.edu.tr

The objective of this study was to evaluate the effects of an adenosine A₁ agonist, phenylisopropyl adenosine (PIA), on metamidophos poisoning compared to specific antidotes. Rats were poisoned with metamidophos (30 mg/kg, oral) and observed for 24 hours. One group received sodium chloride (1 mL/kg) and four experimental groups received atropine (5 mg/kg), pralidoxime (PAM, 20 mg/kg), atropine/PAM (5/20 mg/kg) or PIA (1 mg/kg) intraperitoneally. Atropine reduced salivation and prevented respiratory distress when compared to sodium chloride-treated rats. Treatment with PAM did not cause any suppression of cholinergic signs. Atropine and PAM combination prevented salivation, convulsion and respiratory distress. PIA delayed initial time of the salivation, convulsion and time to death. However, PIA was found ineffective against the metamidophos-induced cholinergic symptoms and mortality. All treatments, except PIA, lead to survival of these animals. Acetylcholinesterase (AChE) activity was not normalized by PIA or PAM. PIA prevented metamidophos-induced diaphragmatic muscle necrosis as much as PAM. In conclusion, a single dose of PIA was unable to protect the rats from metamidophos toxicity. Further studies are needed involving a combination of PAM and/or atropine with repeated doses of PIA to clarify the efficacy of adenosine agonists in OP poisoning.

Key Words: atropine • organophosphate • PAM • phenylisopropyl adenosine (PIA)

Human & Experimental Toxicology, Vol. 24, No. 7, 369-375 (2005)
DOI: 10.1191/0960327105ht540oa


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