title: The alpha 2 adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2 adrenoreceptor antagonist idazoxan promotes seizures: pontine microinfusion studies of amygdala-kindled kittens.
abstract: 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.
authors.affiliation: Sleep Disturbance Research (151A3), VAMC Sepulveda, CA 91343, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Shouse
authors.forename: J
authors.initials: J
authors.lastname: Langer
authors.forename: M
authors.initials: M
authors.lastname: Bier
authors.forename: P R
authors.initials: PR
authors.lastname: Farber
authors.forename: O
authors.initials: O
authors.lastname: Alcalde
authors.forename: R
authors.initials: R
authors.lastname: Moghimi
authors.forename: M
authors.initials: M
authors.lastname: Richkind
authors.forename: R
authors.initials: R
authors.lastname: Szymusiak
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000367:Age Factors; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D019329:Idazoxan / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects; D008839:Microelectrodes; D008845:Microinjections; D009638:Norepinephrine / Q000494:pharmacology; D011149:Pons / Q000187:drug effects / Q000503:physiopathology; D012640:Seizures / Q000188:drug therapy*; D013565:Sympatholytics / Q000494:pharmacology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D013565:Sympatholytics; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan