SUBACUTE TOXICITY OF ALDICARB - PREVENTION AND TREATMENT WITH MEMANTINE AND ATROPINE

Daily administration (i.p.) of aldicarb in male Sprague-Dawley rats at various dosage levels for 21 days revealed 1) 0.1 mg/kg, nontoxic dose; 2) 0.2 mg/kg, moderately toxic dose; and 3) 0.4 mg/kg, severely toxic dose. Inhibition of acetylcholinesterase (AChE) in discrete brain regions and diaphragm muscle was dose dependent. Toxic signs were predominantly peripheral even though AChE inhibition was significantly higher in the brain (except striatum). Besides AChE inhibition, marked inactivation of carboxylesterases (false targets) was observed, suggesting a protective mechanism especially against low dosage by reducing free concentration of aldicarb. After 30 min following the 7th, 14th, or 21 st dose of aldicarb, the degree of inhibition of esterase(s) remained the same, and consequently no tolerance developed to aldicarb. On day 21, administration of memantine HCl (18 mg/kg, i.p.) and atropine sulfate (16 mg/kg, i.p.) 30 min and 15 min, respectively, prior to aldicarb (0.4 mg/kg) injection provided complete protection. Therapeutic administration of these antidotes completely reversed the clinical manifestations of intoxication. The present findings indicated that memantine provided protection and reversal of AChE from inhibition in addition to reversible blockage of hyperneuromuscular activity.