The tricyclic antidepressants are the most effective drugs
presently available for the treatment of depression. These act
by increasing the release of norepinephrine. Amphetamine and
cocaine can also act in this manner.
Imipramine, amitriptylin, and other closely related drugs
are among the drugs currently most widely used for the treatment
of major depression.
The activity of the tricyclic drugs depends on the central
ring of seven or eight atoms which confers an angled or twisted
conformation. The side chain must have at least 2 carbons although
3 appear to be better. The amine group may be either tertiary
All tricyclic antidepressants block the re-uptake of norepinephrine
at nerve terminals. However, the potency and selectivity for
the inhibition of the uptake of norepinephrine, serotonin, and
dopamine vary greatly among the agents. The tertiary amine tricyclics
seem to inhibit the serotonin uptake pump, whereas the secondary
amine ones seem better in switching off the NE pump. For instance,
imipramine is a potent and selective blocker of serotonin transport,
while desipramine inhibits the uptake of norepinephrine.