Is elevated norepinephrine an etiological factor in some cases of epilepsy?
It is well established that the neurotransmitter norepinephrine (NE) has anticonvulsant properties. However, NE may also have proconvulsant properties under some conditions, both in animal epilepsy models and in humans. This paper examines the hypothesis that this neurotransmitter has proconvulsant properties, where much of the pharmaceutical evidence comes from rodent models. In assessing the elevated NE epilepsy hypothesis, the following seven lines of evidence are examined that include studies of: (1) antidepressants that raise the level of NE; (2) clonidine and other alpha 2 adrenergic agonist drugs that lower the level of NE; (3) prazosin and other drugs that affect alpha adrenoceptors; (4) propranolol and other drugs that affect beta adrenoceptors; (5) pheochromocytoma, which is a rare cancer of the adrenal glands that can boost NE levels; (6) comorbidity of epilepsy with bipolar disorder, hypertension, and obesity, where all four conditions may involve elevated NE; and (7) psychological stress, which is associated with increased release of NE. The body of evidence supporting the NE proconvulsant hypothesis is consistent with the notion that elevated, endogenous noradrenergic transmission is an etiological factor in some cases of epilepsy.
Fitzgerald
Paul J
PJ
The Zanvyl Krieger Mind/Brain Institute, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, 338 Krieger Hall, 3400N Charles St, Baltimore, MD 21218, USA. pfitz@mbi.mb.jhu.edu
D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001714:Bipolar Disorder / Q000150:complications; D004827:Epilepsy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000150:complications; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D010673:Pheochromocytoma / Q000150:complications / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018687:Antidepressive Agents, Second-Generation; D009638:Norepinephrine