Uses
Tranquilizer (minor).
Uses
5-Chloro Buspirone is an impurity of Buspirone Hydrochloride (B689850), a non-benzodiazepine anxiolytic and a 5-hydroxytryptamine (5-HT1) receptor agonist.
Uses
Buspirone is an extremely specific drug that could possibly represent a new chemical class
of anxiolytics—azaspirones. As an anxiolytic, its activity is equal to that of benzodiazepines; however, it is devoid of anticonvulsant and muscle relaxant properties, which are
characteristic of benzodiazepines.
Definition
ChEBI: An azaspiro compound that is 8-azaspiro[4.5]decane-7,9-dione substituted at the nitrogen atom by a 4-(piperazin-1-yl)butyl group which in turn is substituted by a pyrimidin-2-yl group at the N4 position.
brand name
Buspar (Bristol-Myers Squibb).
Biological Functions
Buspirone (BuSpar) is the first example of a class of
anxiolytic agents that can relieve some symptoms of
anxiety in doses that do not cause sedation. Buspirone
is structurally unrelated to existing psychotropic drugs.
General Description
The initial compound in this series, buspirone (BuSpar), hasanxiolytic and antidepressant activities and is a partial5-HT
1A agonist. Its anxiolytic activity is reportedly causedby its ability to diminish 5-HT release (via 5-HT
1A agonism).High short-term synaptic levels of 5-HT are characteristic ofanxiety. Also, because it is a partial agonist, it can stimulatepostsynaptic receptors when 5-HT levels are low in thesynapse, as is the case in depression. Several other spironesare in development as anxiolytics and antidepressants.
Mechanism of action
Although buspirone has been shown to interact with a
number of neurotransmitter systems in the brain, it appears
that its clinically relevant effects are mediated
through interactions at the serotonin (5-hydroxytryptamine,
5-HT) 5-HT
1A receptor, where it acts as a partial
agonist.
Pharmacology
Buspirone is as effective as the benzodiazepines in the
treatment of general anxiety. However, the full anxiolytic
effect of buspirone takes several weeks to develop,
whereas the anxiolytic effect of the benzodiazepines is
maximal after a few days of therapy. In therapeutic
doses, buspirone has little or no sedative effect and
lacks the muscle relaxant and anticonvulsant properties
of the benzodiazepines. In addition, buspirone does not
potentiate the central nervous system depression
caused by sedative–hypnotic drugs or by alcohol, and it
does not prevent the symptoms associated with benzodiazepine
withdrawal.
Clinical Use
Buspirone is effective in general anxiety and in anxiety
with depression.
Side effects
Like the benzodiazepines, buspirone appears to be safe
even when given in very high doses. The most common
side effects are dizziness, light-headedness, and headache.
Abuse, dependence, and withdrawal have not been
reported, and buspirone administration does not produce
any cross-tolerance to the benzodiazepines. Buspirone
has been reported to increase blood pressure in
patients taking monoamine oxidase inhibitors, and it
may increase plasma levels of haloperidol if coadministered
with that agent.
Synthesis
Buspirone, 8-[4-[4-(2-pyrimidyl)-1-piperazinyl]butyl]-8-azaspiro [4,5]
decan-7,9-dione (5.2.6), is synthesized by the reaction of 1-(2-pyrimidyl)-4-
(4-aminobutyl)piperazine (5.2.4) with 8-oxaspiro[4,5]decan-7,9-dione (5.2.5). In turn, 1-
(2-pyrimidyl)-4-(4-aminobutyl)piperazine (5.2.4) is synthesized by the reaction of
1-(2-pyrimidyl)piperazine with 4-chlorobutyronitrile, giving 4-(2-pyrimidyl)-1-(3-
cyanopropyl)piperazine (5.2.3), which is hydrogenated with Raney nickel into buspirone
(5.2.4) [51¨C55].
Metabolism
Buspirone is well absorbed from the gastrointestinal
tract, and peak blood levels are achieved in 1 to 1.5
hours; the drug is more than 95% bound to plasma proteins.
Buspirone is extensively metabolized, with less
than 1% of the parent drug excreted into the urine unchanged.
At least one of the metabolic products of buspirone
is biologically active. The parent drug has an
elimination half-life of 4 to 6 hours.
