Geriatric psychiatry:
serotonin specificity as a new approach
Vernon M Neppe MD, PhD
Educational Objectives
- To educate in the area of serotonin and particularly
the serotonin 1A receptor subtype.
- To discuss the clinical implications of the serotonin
1A receptor with regard to management options and
problems.
- To examine the evolution of the new antidepressants
in psychogeriatrics.
- To delineate specific geriatric related problems.
Abstract
The serotonin receptors modulate a variety of basic functions
at a large number of levels. These functions reflect serotonin
1A neuromodulators as well. Because of the low toxicity,
remarkable toleration, significant experience in geropsychiatry
and the medically ill, and the ostensible lack of abuse,
serotonin 1A related compounds have significant potential
application in geriatric psychiatry and medical illness.
Serotonin 1A receptor action can be measured relatively
specifically by the azapirones. These act as partial
agonists postsynaptically and full agonists at the autoreceptor.
Non-specifically, beta2 -adrenergic receptor blockers
(like propranolol) produce overall serotonin 1A receptor
antagonist effects. Beta-blockers have limited application
in the elderly, despite their role of serotonin 1A.
The perspectives in akathisia and aggression may be
relevant. The benzodioxines, an experimental group,
which includes eltoprazine, act as partial agonists
postsynaptically on both 5HT 1A and 1B receptors, and
have potential application in aggression. Particularly
interesting is a possible link of the neural growth
factor S100ß with serotonin 1A and Alzheimer?s
disease.
Specific serotonin modulators are evaluated using the
azapirones as the pharmacologic probe. Buspirone as
the only marketed azapirone is approved for use only
in anxiety and mixed anxiety depressive states, however,
clinical experience in several other areas is interesting.
Low doses of buspirone probably act presynaptically
as anti-aggressive agents and speculatively help akathisia;
medium doses act post-synaptically possibly as antagonists
modulating anxiety; higher doses are weak agonists and
may correspond with weak antidepressant effects, some
modulation of obsessionality, and even possible effects
on the irritability of the manic. Such doses also may
induce mild akathisia: this may imply a serotonin 1A
modulating role, but this is complex as serotonin re-uptake
blockers like fluoxetine which act broadly also induce
akathisia; moreover this can be blocked by buspirone.
Finally extremely high doses of buspirone appear very
promising antitardive dyskinesia agents: as these effects
may be blocked by cyproheptadine, this too may be via
serotonin 1A neuromodulation of the known partial dopamine
agonist effects of buspirone in conventionally supra-therapeutic
doses.
|
