The alpha 2 adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2 adrenoreceptor antagonist idazoxan promotes seizures: pontine microinfusion studies of amygdala-kindled kittens.

This is the first report showing that microinfusion of alpha 2 adrenoreceptor agonists and antagonists into the vicinity of the locus ceruleus (LC) have contrasting effects on evoked amygdala-kindled seizure susceptibility. Microinfusion (1 microliter) of the alpha 2 agonist clonidine (CLON) and of the alpha 2 antagonist idazoxan (IDA) were made over 1 min through cannulae in the LC ipsilateral to the kindled amygdala in 6 kittens. Order of administered drugs (CLON vs. IDA) and dosages (n = 3 each) were partly counterbalanced. Focal and convulsive seizure thresholds were evaluated 10-12 min post-infusion and compared to thresholds obtained during two, interspersed control conditions (vehicle control = 1 microliter microinfusion of sterile saline; sham control = needle insertion only). CLON significantly elevated focal and generalized seizure thresholds, whereas IDA significantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose-dependent. These findings confirm that norepinephrine (NE) is a potent antiepileptic agent. Results also suggest that pontine microinfusions could eventually provide an alternative treatment option for medically refractory limbic epilepsy.