Chapter 14

Buspirone

Introduction
Partial agonist of the 5-HT1A receptor
There is high regional density of 5-HT1A
receptors in midbrain, hippocampus, and limbic
region.
Consistent with the notion that 5-HT
neurotransmission modulates mood and anxiety.
Therefore, drugs targeting this receptor hold
interest for the treatment of mood disorders.

History
Buspirone was synthesized in 1968 in
Mead Johnsons lab.
Originally studied as antipsychotic, but
failed clinically.
However, it had a marked taming effect in
aggressive monkeys.
Anti-anxiety agent.

Pharmacological Profile
Inactive in receptor binding at
noradrenergic, cholinergic and
histaminergic sites.
Dopmine receptor binding is believed to
play no role in therapeutic or side effects.
The antianxiety properties of buspirone
appear to be its actions at both pre- and
postsynaptic 5-HT1A receptors.

Pharmacokinetics and Mechanism

of Action
Oral administration
Half-life of 3-4 hours
prolonged by food ingestion and hepatic/renal
impairment

Metabolites
5-OH-Bu, 8-OH-Bu, 1-PP(1-2-pyrimidinyl piperazine),
6-OH-Bu

1-PP has noradrenergic effects

6-OH-Bu
High affinity & partial agonist activity for the 5-HT1A R
Contributes significantly to the therapeutic effect of
buspirone

Buspirone increases plasma cortisol, prolaction

and growth hormone.

Buspirone VS benzodiazepine

Does not impair psychomotor performance

Lacks abuse potential
Shows anti-depressant like activity
Non-sedating
Spares cognitive and memory functions
But slow in action
But has serotonin syndrome

 Somatic anxiety and psychic anxiety

Ongoing treatment found similar therapeutic
response.
Stopping abruptly after 6 months revealed
BZDs: Relapsed in 4 weeks (withdrawal syndrome)
Buspirone: No symptom changes

Longterm follow up at 40 months after 6 months

medication (Rickels and Schweizer 1990)
BZDs: 50% of patients still required BZDs
Buspirone: None required anxiolytics

Indications and Efficacy

FDA: Generalized Anxiety Disorder
Initial15-20mg/day
Maximum60mg/day

Nonapproved Clinical Indications

PTSD
Other anxiety disorders
Smoking cessation
Depression, adjunctive therapy usually with SSRIs
and SNRIs
May required higher dosage for MDD treatment
(90mg/day)

Side Effects and Toxicology

Dizziness(12%)
Drowsiness(10%)
Nausea(8%)
Headache(6%)
Nervousness(5%)
Fatigue(4%)
Insomnia,light-headedness,dry mouth(3%)
Excitement(2%)
No death yet. Unusually safe, except for
potential serotonin syndrome.

Conclusion
Partial agonist of the 5-HT1A receptor.
Indication: GAD (start with 15-20mg/day,
maximum 30mg/day).
Better than BZDs because of no
dependence or withdrawal effects.
However, no sedation and slower onset.