Mechanism of action of
antidepressant medications
by
Feighner JP
J Clin Psychiatry 1999; 60 Suppl 4:4-11; discussion 12-3
ABSTRACT
The psychopharmacology of depression is a field that has evolved rapidly in just under 5 decades. Early antidepressant medications--tricyclic
antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)--were discovered
through astute clinical observations. These first-generation medications were
effective because they enhanced serotonergic or noradrenergic mechanisms or
both. Unfortunately, the TCAs also blocked histaminic, cholinergic, and
alpha1-adrenergic receptor sites, and this action brought about unwanted side
effects such as weight gain, dry mouth, constipation, drowsiness, and dizziness.
MAOIs can interact with tyramine to cause potentially lethal hypertension and
present potentially dangerous interactions with a number of medications and
over-the-counter drugs. The newest generation of antidepressants, including the
single-receptor selective serotonin reuptake inhibitors (SSRIs) and
multiple-receptor antidepressants venlafaxine, mirtazapine, bupropion,
trazodone, and nefazodone, target one or more specific brain receptor sites
without, in most cases, activating unwanted sites such as histamine and
acetylcholine. This paper discusses the new antidepressants, particularly with
regard to mechanism of action, and looks at future developments in the treatment
of depression.
TCAs
SSRIs
RIMAs
Classes
Relapse
Mirtazapine
Mechanisms
The long wait?
Antidepressants
SSRIs and SNRIs
SSRI mechanisms
Serotonin and dopamine
Acetylcholine and dopamine
Noradrenaline and serotonin
Noradrenaline and dopamine
Comparisons and metabolites
Antidepressants and cell growth
Neuropharmacology of serotonin
Antidepressants and the unexplained
How effective are commonly prescribed antidepressants?
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