| Indication |
For management of depression and for Obsessive Compulsive Disorder
(OCD). Has also been used in the management of bulimia nervosa. |
| Pharmacodynamics |
Fluvoxamine, an aralkylketone-derivative agent, is one of a
class of antidepressants known as selective serotonin reuptake
inhibitors (SSRIs) that differs structurally from other SSRIs. It is
used to treat the depression associated with mood disorders. It is also
used on occassion in the treatment of body dysmorphic disorder and
anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic
actions of Fluvoxamine are presumed to be linked to its inhibition of
CNS neuronal uptake of serotonin. In vitro studies show that
Fluvoxamine is a potent and selective inhibitor of neuronal serotonin
reuptake and has only very weak effects on norepinephrine and dopamine
neuronal reuptake. Fluvoxamine has no significant affinity for
adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic,
histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2),
or benzodiazepine receptors; antagonism of such receptors has been
hypothesized to be associated with various anticholinergic, sedative,
and cardiovascular effects for other psychotropic drugs. The chronic
administration of Fluvoxamine was found to downregulate brain
norepinephrine receptors, as has been observed with other drugs
effective in the treatment of major depressive disorder. Fluvoxamine
does not inhibit monoamine oxidase. |
| Mechanism of action |
The exact mechanism of action of fluvoxamine has not been fully
determined, but appears to be linked to its inhibition of CNS neuronal
uptake of serotonin. Fluvoxamine blocks the reuptake of serotonin at the
serotonin reuptake pump of the neuronal membrane, enhancing the actions
of serotonin on 5HT1A autoreceptors. In-vitro studies
suggest that fluvoxamine is more potent than clomipramine, fluoxetine,
and desipramine as a serotonin-reuptake inhibitor. Studies have also
demonstrated that fluvoxamine has virtually no affinity for α1- or α2-adrenergic, β-adrenergic, muscarinic, dopamine D2, histamine H1, GABA-benzodiazepine, opiate, 5-HT1, or 5-HT2 receptors. |
| Absorption |
Well absorbed, bioavailability of fluvoxamine maleate is 53%. |
| Volume of distribution |
|
| Protein binding |
~77-80% (plasma protein) |
| Metabolism |
Hepatic |
| Route of elimination |
The main human metabolite was fluvoxamine acid which, together
with its N-acetylated analog, accounted for about 60% of the urinary
excretion products. Approximately 2% of fluvoxamine was excreted in
urine unchanged. Following a 14C-labelled oral dose of fluvoxamine
maleate (5 mg), an average of 94% of drug-related products was recovered
in the urine within 71 hours. |
| Half life |
15.6 hours |
| Clearance |
Not Available |
| Toxicity |
Side effects include anorexia, constipation, dry mouth, headache,
nausea, nervousness, skin rash, sleep problems, somnolence, liver
toxicity, mania, increase urination, seizures, sweating increase,
tremors, or Tourette's syndrome. |
