Monoaminergic mechanisms in epilepsy may offer innovative therapeutic opportunity for monoaminergic multi-target drugs
Front. Neurosci.. 2016-11-10; 10:
DOI: 10.3389/fnins.2016.00492
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A large body of experimental and clinical evidence has strongly suggested that
monoamines play an important role in regulating epileptogenesis, seizure
susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in
people with epilepsy (PWE). However, neither the relative significance of
individual monoamines nor their interaction has yet been fully clarified due to
the complexity of these neurotransmitter systems. In addition, epilepsy is
diverse, with many different seizure types and epilepsy syndromes, and the role
played by monoamines may vary from one condition to another. In this review, we
will focus on the role of serotonin, dopamine, noradrenaline, histamine, and
melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will
be reviewed in consideration of the mutual relationship of monoamines with the
other putative neurotransmitters. The complexity of epileptic pathogenesis may
explain why the currently available drugs, developed according to the classic
drug discovery paradigm of « one-molecule-one-target, » have turned out to be
effective only in a percentage of PWE. Although, no antiepileptic drugs currently
target specifically monoaminergic systems, multi-target directed ligands acting
on different monoaminergic proteins, present on both neurons and glia cells, may
represent a new approach in the management of seizures, and their generation as
well as comorbid neuropsychiatric disorders.