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Abstract
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.