Overview: Buspirone an
Anxioselective Neuromodulator
Vernon M. Neppe
Buspirone (BuSpar) belongs to a new chemical subgroup,
previously called the azaspirodecanediones, now referred
to as the azapirones It is the first in the class of
pure anxioselective agents. It differs substantially
in both clinical and pharmacological properties from
the benzodiazepines. Clinically, it does not cause the
sedation, hypnosis, anticonvulsant effects and muscle
relaxation effects of the benzodiazepines, and it takes
several weeks to achieve its maximal therapeutic effects
as an anxiety agent. Consequently, target symptoms such
as decreased agitation, irritability, improved concentration,
and diminished worry should be sought after during its
first weeks of administration. Chemically, the exact
anxioselective effect probably relates to a post-synaptic
partial agonist effects at the serotonin 1A receptor
at usual therapeutic doses (30-60 mg per day). At higher
supratherapeutic doses it has a partial agonist dopaminergic
effect. Its action initially is as a pure agonist at
the autoreceptor raphe nucleus level; its post-synaptic
effect impacts several strategic areas - limbic system,
hippocampus, amygdala, cerebral cortex and even neuroglia.
There are no significant neuro-endocrine effects of
therapeutic doses, and the drug has no antipsychotic
effects. Eleven major research studies, including nine
double-blind studies of buspirone versus diazepam or
chlorazepate, have shown equal efficacy with less untoward
side effects and a marked superiority compared with
placebo after four weeks of treatment for generalized
anxiety disorder. This bears out the anxiety paradigm
studies in experimental animals. The anxiolytic action
may be an effect of either the parent drug or its metabolite,
1- 2- pyrimidinyl piperazine (1PP) or both. Studies
in both man and animals suggest buspirone should not
induce physical or psychological dependence, and drug
reactions with other psychotropics are under study.
It does not significantly interact with propranolol,
but may slightly raise levels of haloperidol. It is
possible that it could be effective in the prophylaxis
of panic disorder, tardive dyskinesia, in the management
of hostility, and of obsessionality. These are all areas
for future research.
Keywords
1- (2-pyrimidinyl) piperazine (1-PP), Anxioselectivity,
Azaspirodecanedione, Azapirone, Buspirone, Buspirone
neuropharmacology (animal, man), Dependence - buspirone,
Intrinsic dopaminergic activity, modulation, Non-benzodiazepine
anxiolytic, Pharmacokinetics of buspirone, Serotonin-mimetic
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