Efficacy of an adenosine A1 receptor agonist compared with atropine and pralidoxime in a rat model of organophosphate poisoning.
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.
Kalkan
S
S
Department of Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Ergur
B U
BU
Akgun
A
A
Kaplan
Y C
YC
Kinay
A O
AO
Tuncok
Y
Y
D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage; D002801:Cholinesterase Reactivators / Q000008:administration & dosage; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology; D004347:Drug Interactions; D007306:Insecticides / Q000506:poisoning*; D008297:Male; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009946:Organothiophosphorus Compounds / Q000506:poisoning*; D010660:Phenylisopropyladenosine / Q000008:administration & dosage / Q000494:pharmacology*; D011041:Poisoning / Q000097:blood / Q000401:mortality; D011220:Pralidoxime Compounds / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D015996:Survival Rate; D013997:Time Factors
D058907:Adenosine A1 Receptor Agonists; D000931:Antidotes; D002801:Cholinesterase Reactivators; D007306:Insecticides; D018727:Muscarinic Antagonists; D009946:Organothiophosphorus Compounds; D011220:Pralidoxime Compounds; D010660:Phenylisopropyladenosine; D001285:Atropine; C014655:methamidophos; D002802:Cholinesterases; C028797:pralidoxime