Abstract
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, α-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 α-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 (\(\bar X\)sessions to stage 5 seizures=8.6±1.16, 10.15±1.04 and 8.5±0.95, respectively) relative to controls (\(\bar X\)=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 (\(\bar X\)=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 α-2 activity of formamidines as a primary contributor to formamidine toxicity.
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Although the research described in this article has been supported by the United States Environmental Protection Agency (through contract 68-02-4450 to NSI-Environmental Sciences), it has not been subjected to Agency review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. Mention of trade names or commerical products does not constitute endorsement or recommendation for use
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Gilbert, M.E., Mack, C.M. Enhanced susceptibility to kindling by chlordimeform may be mediated by a local anesthetic action. Psychopharmacology 99, 163–167 (1989). https://doi.org/10.1007/BF00442802
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DOI: https://doi.org/10.1007/BF00442802