Premenstrual Syndromes : PMS and PMDD - Rutuja :: The site ...

Trp 5-HTP 5-HT
TrypOHase L-AADC
Presynaptic element
MAO
VMAT
Plasma membrane
transporter (SERT)
MHPG
treatment of depression, were not useful for the treatment
of PMS. These agents are not selective for serotonin.
Also, SSRIs increase serotonin acutely,
particularly in the region of the 5-HT 1A autoreceptor,
but there is a 3–8 week delay for the antidepressant
effect of the serotonin-augmenting drugs when used for
the treatment of depression, but not however for PMS
and PMDD. 77,78 The delayed treatment response in
affective disorder has been explained by the neurotransmitter
receptor theory, suggesting that monoamine
depletion results in 5HT receptor up-regulation and
symptoms of depression. Prolonged drug exposure
would then be necessary to desensitize the 5-HT 1A
autoreceptors and to down-regulate postsynaptic
5HT
Glial cell
5HT
NEUROTRANSMITTER PHYSIOLOGY 73
Release-modulating
autoreceptor
Postsynaptic receptor
Figure 9.3 Basic neurophysiology of a serotonergic neuron. (Reprinted from Deutch and Roth, 16 Section II,
Chapter 7, page 177. © 2002, with permission from Elsevier.)
receptors. A neurophysiological explanation for the
rapid response to SSRIs in PMDD remains unknown.
5-HT postsynaptic receptors are classified into four
subtypes, 5-HT 1 to 5-HT 4 , with further subdivision of
the 5-HT1 subtypes: 79 the most important for mood regulation
include the 5-HT 1A , 5-HT 2A , and 5-HT 2C . 80–82
The 5-HT 3 receptor is especially important as a chemoreceptor
that controls emesis, and 5-HT 3 and 5-HT 4
receptors help to regulate gastrointestinal motility and
appetite. 83,84 Side effects of serotonergic drugs such as
SSRIs are generally related to the stimulation of the
5-HT 2A, 2C, 3, and 4 receptor subtypes. Acute stimulation
of 2A and 2C receptors in various brain and
peripheral regions can lead to agitation, restlessness,