Enhanced susceptibility to kindling by chlordimeform may be mediated by a local anesthetic action

✍ Scribed by M. E. Gilbert; C. M. Mack

• Book ID: 104776161
• Publisher: Springer
• Year: 1989
• Tongue: English
• Weight: 644 KB
• Volume: 99
• Category: Article
• ISSN: 0033-3158
• DOI: 10.1007/bf00442802

✦ Synopsis

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, e-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 ~-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 (J?sessions to stage 5 seizures= 8.6 -t-l .16, 10.15_+1.04 and 8.5_+0.95, respectively) relative to controls (J?=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 (J?=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 c~-2 activity of formamidines as a primary contributor to formamidine toxicity.