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The exact mechanism of action is not well understood,
however it is generally thought that tricyclic antidepressants
work by inhibiting the re-uptake of the neurotransmitters
norepinephrine, dopamine, or serotonin by nerve cells.
Tricyclics may also possess an affinity for muscarinic
and histamine H1 receptors to varying degrees. Although
the pharmacologic effect occurs immediately, often the
patient's symptoms do not respond for 2 to 4 weeks.
Although norepinephrine and dopamine are generally considered
stimulatory neurotransmitters, tricyclic antidepressants
also increase the effects H1 histamine, and thus most
have sedative effects.
Chemistry of re-uptake inhibitors
The chemical action of re-uptake inhibitors in general
was unknown for a long time. In August 2007, two research
groups independently reported that the tricyclic molecule
docks to the transporter protein in a cavity adjacent
to where the neurotransmitter substrate binds, locking
the substrate in place and thereby obstructing re-uptake
transport.
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