Monoaminergic and histaminergic strategies and treatments in brain diseases
Front. Neurosci.. 2016-11-24; 10:
DOI: 10.3389/fnins.2016.00541
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The monoaminergic systems are the target of several drugs for the treatment of
mood, motor and cognitive disorders as well as neurological conditions. In most
cases, advances have occurred through serendipity, except for Parkinson’s disease
where the pathophysiology led almost immediately to the introduction of dopamine
restoring agents. Extensive neuropharmacological studies first showed that the
primary target of antipsychotics, antidepressants, and anxiolytic drugs were
specific components of the monoaminergic systems. Later, some dramatic side
effects associated with older medicines were shown to disappear with new chemical
compounds targeting the origin of the therapeutic benefit more specifically. The
increased knowledge regarding the function and interaction of the monoaminergic
systems in the brain resulting from in vivo neurochemical and neurophysiological
studies indicated new monoaminergic targets that could achieve the efficacy of
the older medicines with fewer side-effects. Yet, this accumulated knowledge
regarding monoamines did not produce valuable strategies for diseases where no
monoaminergic drug has been shown to be effective. Here, we emphasize the new
therapeutic and monoaminergic-based strategies for the treatment of psychiatric
diseases. We will consider three main groups of diseases, based on the evidence
of monoamines involvement (schizophrenia, depression, obesity), the
identification of monoamines in the diseases processes (Parkinson’s disease,
addiction) and the prospect of the involvement of monoaminergic mechanisms
(epilepsy, Alzheimer’s disease, stroke). In most cases, the clinically available
monoaminergic drugs induce widespread modifications of amine tone or excitability
through neurobiological networks and exemplify the overlap between therapeutic
approaches to psychiatric and neurological conditions. More recent developments
that have resulted in improved drug specificity and responses will be discussed
in this review.