Effects of some calcium modulators on monensin toxicity

Monensin is extremely toxic to some domestic animals, like the equine species, if they ingest poultry or cattle rations containing the drug. From a treatment standpoint, no specific compounds are known to alleviate or interact with monensin. Effects of some cardiovascular drugs which antagonize calcium influx in cardioskeletal and smooth muscles were evaluated in mice receiving varying lethal doses (80, 100, 120 or 140 mg/kg ip). Calcium channel blockers (verapamil, diltiazem and lidocaine), a calmodulin antagonist (chlorpromazine), adrenergic receptor blockers (yohimbine, tolazoline and propranolol), and a cardiac glycoside (digoxin) were evaluated for their effects on monensin toxicity following their 30 min pretreatments in mice ip. All the calcium modulators evaluated apart from chlorpromazine, propranolol, and digoxin, potentiated monensin toxicity significantly (p less than 0.05) by decreasing the calculated LD50 of monensin (108 mg/kg); the latter 3 drugs had no effect on monensin toxicity. This study suggests that excess calcium ion influx may not be the only factor responsible for monensin toxicosis in mice.