Clinical Overview of Serotonin 1A Relationships of Agitation,
Aggression, Anxiety and Mood
Educational Objectives
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To educate in the area of clinical links of the serotonin 1A
receptor subtype.
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To discuss the clinical implications of the serotonin 1A
receptor with regard to management options and problems.
Abstract
The serotonin receptors modulate a variety of basic psychological
and behavioral functions. These functions may reflect serotonin 1A
neuromodulation as well. The serotonin 1A receptor subtype is unique
because it is found at the raphe nuclei level as the serotonin
autoreceptor as well as post-synaptically in areas linked with
limbic function. This may imply differential effects at different
doses. Because of the low toxicity and receptor specificity of
serotonin 1A related compounds their potential application in
psychiatry and medicine is substantial.
Several drug groups modulate serotonin 1A receptor action.
Non-specifically, beta-2-adrenergic receptor blockers (like
propranolol) produce overall serotonin 1A receptor antagonist
effects. The benzodioxines, an experimental group, which includes
eltoprazine, act as partial agonists postsynaptically on both
5HT 1A and 1B receptors. Lithium cation is very non-specific but
does impact the serotonin 1A receptor. Serotonin 1A receptor
action can be measured relatively specifically by the azapirones
which act as partial agonists postsynaptically and full agonists
at the autoreceptor.
Beta-blockers have impacts on agitation, aggression, anxiety
and depression. The effects appear bimodal, at lower dosage
probably reflecting a peripheral beta-adrenergic blockade and at
higher doses possibly reflecting post-synaptic serotonin 1A
antagonism.
The benzodioxines are being researched specifically in aggression
and may have a role in modulating serotonin 1A.
Agitation, aggression, anxiety and mood all are implicated in
azapirone function. The azapirones can be used as a pharmacologic
probe because these effects appear to be dose dependent, in part,
and because of the specificity at serotonin 1A. At this point,
most of the research has been performed on buspirone as the only
marketed azapirone. It is FDA approved for use only in
generalized anxiety and mixed anxiety depressive states, however,
clinical experience in several other areas is interesting. Low
doses of buspirone probably act presynaptically as may be
applicable in irritability and lesser agitation; medium doses
act post-synaptically possibly antagonizing excess serotonin 1A
modulating anxiety; higher doses are weak agonists and may
correspond with limited antidepressant effects and some modulation
of obsessionality. Doses of the order of 60mg and beyond
tentatively have possible effects on the irritability, confrontation
and anger of the manic, although not effecting psychosis or
sleep-this may imply a serotonin 1A agonist modulating role.
The scanty literature is discussed.
From these approaches, a unified theory linking agitation,
aggression, anxiety and mood with the serotonin receptor 1A
subtype and its cross-talk with other receptors can be
developed.
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