CHEMISTRY OF THE BRAIN: MOLECULES, MOOD, AND MENTAL ILLNESS - Chemistry: Notable Research and Discoveries - page 86

neurotransmitters are available. In 1958, many physicians and psychia-
trists began using iproniazid as a treatment for depressive illness.
Reserpine and iproniazid research led to the monoamine hypoth-
esis of depression. This hypothesis proposed that a reduction in the
monoamine neurotransmitters caused depression. As described in the
sidebar on pages 82-83, only a small number of neurons use serotonin
as a neurotransmitter, but these cells project to widespread regions of
the brain. The same holds true for norepinephrine and dopamine. Al-
though not widely used in the nervous system, these neurotransmitters
are apparently involved in networks of neurons that greatly influence a
person's mood. Synaptic transmission between neurons in other areas
of the brain—such as neurons that process visual information, for in-
stance—often carry specific messages, such as the presence of an object
at a certain point in the person's visual field. In contrast, the mono-
amine neurotransmitters underlie information processing of a more
general nature, some of which correlates with mood.
Because iproniazid had serious side effects, including a dangerous
increase in blood pressure, researchers began looking for other anti-
depressant medications. Soon they found a class of drugs that became
known as tricyclic antidepressants, named for the molecule's three ring-
shaped structures. The first such drug was imipramine, developed in
the late 1950s. Among other effects, tricyclic antidepressants inhibit the
reuptake of serotonin and norepinephrine, which leaves more time for
these neurotransmitters to act on the postsynaptic neuron. This mecha-
nism is in accordance with the monoamine hypothesis.
Tricyclic antidepressants are still prescribed today, but some pa-
tients experience side effects such as dry mouth, blurry vision, constipa-
tion, and other uncomfortable conditions. Other antidepressants have
since been found that induce fewer side effects. One of the most popu-
lar is fluoxetine, which is marketed under the trade name Prozac. This
drug, along with Zoloft and other antidepressants, are known to inhibit
reuptake proteins specifically for serotonin. As a result, these drugs are
called selective serotonin reuptake inhibitors, or SSRIs. Although some
concerns have appeared because of a possible risk of suicide in young
patients who take Prozac, these drugs are commonly prescribed and
have proved highly effective in millions of patients.
Even before the development of SSRIs in the 1980s, some research-
ers focused on serotonin as the most important monoamine involved