Enhanced susceptibility to kindling by chlordimeform may be mediated by a local anesthetic action.
The formamidine pesticides amitraz and chlordimeform have recently been shown to be potent proconvulsants (Gilbert 1988). Two main neuroactive properties have been identified as mediators of formamidine neurotoxicity, alpha-2 adrenergic agonism and local anesthetic actions. These two proposed mechanisms of formamidine action were contrasted using electrical kindling of the amygdala. Male rats were administered 0, 10 and 40 mg/kg of the local anesthetic lidocaine, 0, 0.01 and 0.10 mg/kg of the alpha-2 adrenergic agonist clonidine or 0, 10 and 30 mg/kg chlordimeform, IP, once per day. After each injection, kindling stimulation was delivered through chronically-implanted electrodes. The high dosage of chlordimeform and both dosages of lidocaine enhanced the rate of kindling development (mean sessions to stage 5 seizures = 8.6 +/- 1.16, 10.15 +/- 1.04 and 8.5 +/- 0.95, respectively) relative to controls (mean = 14.59 +/- 1.36). Afterdischarge (AD) durations were increased over the first seven sessions by both treatments, but the total cumulative AD did not differ from controls. Clonidine, by contrast, delayed kindling development (mean 27.57 +/- 1.97) and shortened the mean AD duration over the first seven sessions. These data provide support for a local anesthetic action of chlordimeform and stand in contrast to several recent demonstrations of alpha-2 activity of formamidines as a primary contributor to formamidine toxicity.
Gilbert
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NSI Environmental Sciences, Research Triangle Park, NC 27709.
Mack
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D000578:Amidines / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002742:Chlorphenamidine / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004569:Electroencephalography; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D000578:Amidines; D000779:Anesthetics, Local; D002742:Chlorphenamidine; D003000:Clonidine