Indication:
Anxiety
Summary-
Gepirone is a nonbezodiazepine drug similar instructure to buspirone. It lacks the sedative
and adverse psychomotor and memory impairment effects of the bezodiazepines and
does not appear to have the potential for causing physical dependence or addiction.
Gepirone selectively affects the serotonergic system, targeting specifically the serotonin
5-HT1A receptor subtype. Clinical studies indicate that it possesses both antiaxiety
and antidepressant properties and is well tolerated.
Gepirone is currently in phase II/ III clinical trials and will be available from Bristol Myers
Squibb. An anticipated approval date is unknown.
Adverse Reaction:
Side effects-
Gepirone is well tolerated with most side effects reported as mild to moderate. The most
frequently reported adverse effects were dizziness, nausea, headache, drowsiness, and
weakness.
Gepirone does not impair memory, verbal fluency, or psychomotor performance.
Like buspirone, gespirone does not appear to have a potential for causing physical
dependence or addition in humans, and it is expected that gepirone will not interact
with alcohol or sedative/hypnotic drugs.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Gepirone an azapirone, is chemically related to buspirone (Buspar) but unrelated to the
benzodiazipines in structure or pharmacology. Gepirone does not directly or indirectly
interact with the benzodiazepine-GABA receptor-chloride ion channel complex. Differing
from buspirone , gepirone does not interact with dopamine receptors. It principle effect
relates to its action on brain serotinin activity.
The biochemical basis of psychiatric disorders of anxiety or depression may be viewed
as a dynamic serotonergic continutation with anxiety representing a relative a 5-HT1
defecit disease. Gepirone acts as total agonist on presynaptic 5-HT, A autoreceptors
(inhibit neuronal firing and decrease 5-HT synthesis) and as a partial agonist at
postsynaptic 5-HT1 A receptors ( linked to cyclic -AMP and probably modulate signal
tranfer)
Pharmacokinetics-
Gepirone is rapidlly absorbed after oral administration , reaching peak levels in about
1 hour. It undergoes extensive first pass metabolism by the liver and has an oral
bioavailability of only 15%. Both it and buspirone are hepatically metabolised to the
major active metabolite 1-(2-pyrimidinyl piperazine ) 1-PP.
The plasma half life of gepirone is 2 to 3 hours. No change in dosing would be anticipated
in patients with renal insufficiency or failure.
Clinical trials-
Gepirone 30 to 60mg/day and placebo were compared in a 6 week double blind trial in 30
outpatients with generalized anxiety disorder. According to various scales, gepirone was
significantly superior to placebo and produced improvement in both somatic and psychic
anxiety.
Significant improvement was delayed and occurred after 2 to 3 weeks of treatment.
Predictors of clinical improvement included high levels of baseline activity and length
of time off anxiolytic therapy( ie. longer the time off benzodizepines etc.. the more
likely a positive response.)
Both a single blind study using doses of 25 to 75mg/day and a double blind , placebo
controlled study using doses ranging from 5 to 90mg/day found gepirone exerted
significant antidepressant effects in patients with major depression
Manufacturer Details