5-HT (serotonin) is a neurotransmitter found in the brain and periphery that plays an important role in platelet function and various disorders. It is synthesized from tryptophan via tryptophan hydroxylase and stored in platelets and neurons. Degradation occurs via monoamine oxidase A. There are multiple 5-HT receptor subtypes located throughout the body. 5-HT is involved in gastrointestinal motility, smooth muscle contraction, vascular effects, platelet aggregation, and various central nervous system functions. Disorders related to abnormal 5-HT include migraine, carcinoid syndrome, and pulmonary hypertension.

2. OVERVIEW
 5-HT is an important neurotransmitter present in both brain
and periphery .it is local hormone and actively play vital role
in platelet function .
 The pathophysiology can cause the different disorders such as
migraine ,pulmonary hypotension and carcinoid syndrome
Entaramine
in gut
Serotonin in
blood

3. INTRODUCTION
 5-HT also called as serotonin.
 Terms ‘5-HT’ and ‘serotonin’ are used interchangeably. 5-HT was
subsequently found in the central nervous system (CNS) and shown
to function both as a neurotransmitter and as a local hormone in the
peripheral vascular system .

4. DISTRIBUTION,BIO SYNTHESIS AND DEGREDATION
Endogenous of 5-HT is arises from Biosynthetic pathway similar to noradrenaline except
the precursor amino acid of tryptophan instead of tyrosine
tryptophan
5-HT
tryptophan
Tryptophan hydroxylase
 The 5-hydroxytryptophan is then decarboxylated to 5-HT
by the ubiquitous L-aromatic acid decarboxylase, which
also participates in the synthesis of catecholamines and
histamine Platelets (and neurons) possess a high-affinity
5-HT uptake mechanism.
 They become loaded with 5-HT as they pass through the
intestinal circulation, where the local concentration is
relatively high. Because the mechanisms of synthesis,
storage, release and reuptake of 5-HT are very similar to
those of noradrenaline, many drugs affect both processes
indiscriminately However, selective serotonin reuptake
inhibitors (SSRIs) have been developed and are important
therapeutically as anxiolytics and antidepressants
 5-HT is often stored in neurons and chromaffin cells as a
transmitter, together with various peptide hormones, such
as somatostatin, substance P or vasoactive intestinal
polypeptide.
Degradation of 5-HT occurs mainly through oxidative
deamination, catalyzed by monoamine oxidase A, followed
by oxidation to 5-hydroxyindoleacetic acid (5-HIAA), the
pathway again being the same as that of noradrenaline
catabolism. 5-HIAA is excreted in the urine and serves as
an indicator of 5-HT production in the body.

5. ACTION AND FUNCTION OF ATHEROSCLEROSIS
 Increased gastrointestinal motility (direct excitation of smooth muscle
and indirect action via enteric neurons)
 Contraction of other smooth muscle (bronchi, uterus
 Mixture of vascular constriction (direct and via sympathetic
innervation) and dilatation (endothelium dependent)
 Platelet aggregation and stimulation of nociceptive nerve endings
 Physiological role such as appetite,sleep, mood and hallucinations

6. Serotonin receptors
There are seven families (5-HT1–7) and further subtypes of 5-HT1 (A–F)
and 5-HT2 (A–C) but all are belongs are GPCR family except 5-HT3.
5-HT1 is located in CNS Some effects are mediated through inhibition of
adenylyl cyclase, include neural inhibition and vasoconstriction.
5-HT2 receptors occur in the CNS and many peripheral sites (especially
blood vessels, platelets, autonomic neurons). Neuronal and smooth
muscle effects are excitatory and some blood vessels are dilated as a
result of nitric oxide release from endothelial cells.
5-HT3 receptors occur in the peripheral nervous system, especially
nociceptive afferent neurons and enteric neurons, and in the CNS.
Effects are excitatory, mediated through direct receptor-coupled ion
channels

7.  5-HT4 receptors occur mainly in the enteric nervous system Effects
are excitatory, through stimulation of adenylyl cyclase, causing
increased gastrointestinal motility
 5-HT5 receptors (one subtype in humans) are located in the CNS
 5-HT6 receptors are located in the CNS and on leukocytes.
 5-HT7 receptors are located in the CNS and the gastrointestinal tract.

8. Pharmacological effects
• Gastrointestinal
• Smooth muscle
• Blood vessels
• Platelets
• nerve endings
• Central nervous systm

9. Classification of 5-HT
5-HT 1d antagonist –sumatriptan[ all triptans]
5-HT 2 antagonist methylsergide,
kitenserine
5-HT3 antagonist –ondansetron,
palonosetron
5HT 4 antagonist –metoclopramide ,
cisapride

10.  Migraine can be episodic
 when the attacks are relatively infrequent, or chronic, when the
frequency and severity become a major burden to the patient and is
possibly accompanied by comorbidities such as gastrointestinal
problems or mental health issues.

11. Pathogenesis of migraine
5-HT
Vascular
endothelium
5HT 2 antagonist
NO
VASODIALTION
Trigminovascular nerve
endings
Neuropeptide
release,CGRP
5HT 1B/D/F antagonist
botulinum toxin
Pain
Neuroinflammation
Release of
prostaglandin

13. Carcinoid syndrome
 Carcinoid syndrome is a rare disorder associated with malignant
tumours of enterochromaffin cells.
 These tumors secrete a variety of chemical mediators: 5-HT is the
most important, but neuropeptides such as substance P and other
agents such as prostaglandins and bradykinin are also produced .
 The sudden release of these substances (carcinoid crisis) into the
bloodstream results in several unpleasant symptoms, including
flushing, abdominal cramps, diarrhea, bronchoconstriction and
hypotension.

14. Clinical use of carcinoid syndrome
5-HT2 antagonists, and the mixed 5-HT/histamine antagonist
cyproheptadine, are effective in controlling some of the symptoms of
carcinoid syndrome, but a more useful drug is octreotide (a long-acting
agonist at somatostatin receptors which suppresses hormone secretion
from neuroendocrine, including carcinoid, cells.

15. Pulmonary hypertension
it is extremely serious disease caused by progressive remodelling of
narrowing of vascular trees
There are several types of pulmonary hypertension and the role of 5-HT
was suggested by the fact that at least one form of the condition was
precipitated by appetite suppressants (e.g. dexfenfluramine and
fenfluram