1. Faraza Javed
Mphil Pharmacology

2. Serotonin Receptors
Serotonin receptors or 5- Hdroxytryptamine
is a monoamine neurotransmitter.
Serotonin is found in
 GIT
 Platelets
 CNS

3.  Approximately 90% of the human body's
total serotonin is located in
the enterochromaffin cells in the alimentary
canal (gut), where it is used to regulate
intestinal movements.
 The remainder is synthesized
in serotonergic neurons of the CNS, where it
has various functions. These include the
regulation of mood, appetite, and sleep.

4.  Serotonin secreted from the
enterochromaffin cells eventually finds its
way out of tissues into the blood. There, it is
actively taken up by blood platelets, which
store it. When the platelets bind to a clot,
they release serotonin, where it serves as
a vasoconstrictor and helps to regulate
hemostasis and blood clotting.

5. Biosynthesis
Biosynthesis of serotonin begins with
hydroylation of an essential amino acid L-
Tryptophan. L-Tryptophan is transported
through the BBB into the brain using the
neutral amino acid transmitter on which
competes with other aminoacids-
phenylalanine, leucine and methionine.
Tryptophanhydoxylase is the 1st step and
speed limiting factor of 5-HT synthesis.

6. This enzyme was found in the brain only in
serotogenic neuron. It enable the
conversion of tryptophan into 5- hydroxy
tryptophan, followed by the
decarboxylation mediated by L- amino acid
decarboxylase onto 5- hydroxytryptamine
(serotonin).

8. Receptors Types

10. 5-HT1 Receptors
This group consist of 5 receptor subtypes:
o 5-HT1A
o 5-HT1B
o 5-HT1D
o 5-HT1E
o 5-HT1F

11. 5-HT1A Receptors
This is the most extensively distributed of
all 5-HT receptors. In CNS, these
receptors are present in high density in
cerebral cortex, hippocampus, septum,
amygdala and raphe nucelus, but they
are proven in small amounts in basal
ganglia and thalamus as well.

12. They are involved in the inhibition of
discharge of neurons, regulation of
production of behaviour and eating. They
play an important role in the emergence of
anxiety. They also exert some effects on
CV system.

13. Receptors Effects &
Function
Agonist Antagonist
5-HT1A CNS: Agression,
Anxiety, Appitite,
Memory, Mood
CVS:
Vasoconstriction
, BP, HR
Buspiron,
Ergotamine,
Yohimbine,
Alprenolol,
Pindolol,
Propranolol

14. 5-HT1B Receptors
o They are present in CNS where they induce
presynaptic inhibition and behavioural effects.
They exhibit vascular effects as well, such as
pulmonary vasoconstriction.
o Discovery of antimigraine properties of
Sumatriptan (non-selective 5-HT1D/1B
agonist) increased intrest in this sub type of
receptors.

15. Receptor Effects &
Function
Agonist Antagonist
5-HT1B CNS: Aggression,
Anxiety, Learing,
Locomotion,
Memory, Mood
Vessels:
Pulmonary
Vasoconstriction
Ergotamine,
Dihydroergotamin
e, Sumatriptan,
Zolmitriptan
Yohimbine,
Propranolol,
Pindolol

16. o Expression of 5-HT1D receptor is very low
as compared to 5-HT1B and their clinical
significance still largely unknown.
o The function of 5-HT1E receptor is unknown
but it is hypothesized that they are involved
in regulation of memory.
o 5-HT1F receptor has possible role in
vascular contraction. Distribution in brain
appears limited.

17. Recetors Effects &
Function
Agonist Antagonist
5-HT1D CNS:
Locomotion,
Anxiety
Sumatriptan,
Ergotamine,
Yohimbine
Methiothepin
5-HT1E CNS: Memory -- --
5HT1F BV:
Vasoconstrictio
n
-- --

18. 5-HT2 Receptors
This class has 3 sub types:
o 5-HT2A
o 5-HT2B
o 5-HT2C

19. 5-HT2A Receptors
This receptor type is expressed in many central
and peripheral tissues. This subtype show
increased platelet aggregation and increased
capillary permeability following exposure to
serotonin. In CNS, these receptors are mainly
present in basal ganglia.
5-HT2A antagonist are being developed for the
treatment of schizophrenia.

20. 5-HT2B Receptors
Activation of 5-HT2B receptors leads to the
contraction of smooth muscle of fundus.
Direct injection of selective agonist
BW723C86 in amygdala have anxiolytic
effcets in rats.
Antagonist of these receptors are relatively new
and may find clinical application in the
treatment and prevention of Migraine.

21. 5-HT2C Receptors
These receptors may found in hippocampus
and substantia nigra. Due to lack of selective
ligands for 5HT2C receptors the knowledge
of its action remains unclear.

22. Receptors Effcets &
Function
Agonist Antagonist
5-HT2A CNS: Anxiety,
Imagination,
Learning,
Perception
SM: Contraction
Platelet:
Aggregation
Yohimbine Aripiprazole,
Clozapine,
Olanzapine,
Trazodone
5-HT2B CNS: Anxiety
GIT: GI Motility
Norfenfluramine Agomelatine
5-HT2C CNS: Mood,
Sleep, Anxiety
-- Clozapine,
Olanzapine

23. 5-HT3 Receptors
With the exception of the 5-HT receptor, a ligand-
gated ion channel, all other serotonin
receptors are G protein-coupled receptors that
activate an intracellular second messenger
cascade to produce an excitatory or inhibitory
response. The 5-HT receptor antagonist suppress
vomiting and nausea by inhibiting serotonin
binding to the 5-HT receptors.

24. 5-HT4 Receptors
These receptors are found on CNS and
Myenteric neurons. Prucalopride (brand
name Resolor, developed by Johnson &
Johnson) is a drug acting as a selective, high
affinity 5-HT receptor agonist which targets
the impaired motility associated with chronic
constipation, thus normalising bowel
movements.

25. 5-HT5 Receptors
Rodents have been shown to possess two
functional 5-HT5 receptor subtype, 5-HT5A
and 5-HT5B. Pharmacological function of
these receptors are unknown. Based on their
localization, it has been speculated that they
may be involved in motor control, anxiety,
learning, adaptive behaviour and brain
development.

26. 5-HT6 Receptors
The exact clinical significance of these
receptors remain still unclear. Selective
antagonist of this type of serotonin receptor
have an impact on behaviour and seem to
improve the spatiel memory of laboratory
animal.

27. 5-HT7 Receptors
5-HT7 receptors are expressed abundantly in
the vessels and are responsible for
persistant vasodilation of anesthesized
experimental animal. 5-HT7 receptors are
also expressed in CNS and in smooth
muscles (in GIT tract).

28. Future Aspects
Serotonin is unique among the monoamines in
that its effects are subserved by distinct G-
protein-coupled receptors and one ligand-
gated ion channel. In the last two decades, a
vast amount of new information has become
available concerning the various 5-HT
receptor types and subtypes, and their
characteristics. It still remains to be seen
which functions some of the many subtypes
play in health or disease.

29. The challenge for the next years of serotonin
research is to clear to what extent diversity
in receptors fulfils specific physiological or
pathophysiological roles.
The research may then assist in designing
drugs with an adequate profile at the target
organ and specific disease.