Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721
Physiological and pathological role of
serotonin
A seminar as a part of curricular requirement for 1 year
M.Pharm 1 semester
Presented by
k.Firdous banu
(20L81S0105)
Under the Guidance /Mentorship of
A.Sudheer M. Pharm
Associate professor department of pharmacology

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 2
Contents :
• Autocoids
• Classification
• Serotonin introduction
• synthesis
• Serotonergic receptors
• Physiological actions
• Pathophysiological role

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 3
AUTOCOIDS
 Auto means self and Akos means remedy.
Autacoids can be released by various stimuli.
when released they bring about many physiological
changes such as reddening of the skin, pain, itching,
bronchospasm, etc. These effects can sometimes be
undesirable and cause death.
To prevent these autacoids antagonists are used.

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 4
Classification
• 1) Decarboxylated amino acids:
a) Histamine
b) Serotonin
• 2) Polypeptide:
a) Angiotensin
b) Plasmakinin
c) Vasopressin
• 3) Lipid derived:
a) Leukotrienes
b) Thromboxanes
c) Prostaglandins

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 5
Serotonin
• Serotonin is a monoamine neurotransmitter biologically
derived from tryptophan.
• Structurally it contain indole ring , hydroxyl group and ethyl
amine group attached to the ring.

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• Approximately 90% of the human body's total
serotonin is located in the enterochromaffin cells in the
GI tract.
• About 8% is found in platelets and 1–2% in the CNS.
• Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver.

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Synthesis

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Types of serotonin receptors:
5-HT1- 5-HT7
• All are GPCRs expect 5-HT3(it is a ligand gated Na+channel).
• All are cAMP expect 5-HT2.
• 5-HT1 Inhibit cAMP and 5-HT4, 5-HT6 and 5HT7 increases cAMP.
Serotonergic receptors

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 9

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 10

RIPER
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SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 11

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 12
1. CVS :
 It constrict large vessels , dilates arterioles.
 BP: a triphasic response is classically seen on i.v. injection of 5-HT in
animals.
• Early sharp fall in BP—due to coronary chemoreflex.
• Brief rise in BP—due to vasoconstriction and increased cardiac
output.
• Prolonged fall in BP—due to arteriolar dilatation and extravasation
of fluid.
Pharmacological actions

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2. Visceral smooth muscles :
 Peristalsis is increased and diarrhoea can occur.
 It constricts bronchi, but is less potent than histamine.
3. Glands :
 5-HT inhibits gastric secretion (both acid and pepsin), but increases
mucus .
It thus has ulcer protective property.
4. Nerve endings and adrenal medulla:
Afferent nerve endings are activated causing tingling and pricking
sensation, as well as pain.

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5. Platelets :
By acting on 5-HT2A receptors 5-HT causes changes in shape of
platelets, but is a weak aggregator.
6. CNS :
 Direct injection in the brain produces sleepiness, changes in body
temperature, hunger and a variety of behavioural effects.

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1.Neurotransmitter :
5-HT appears to be involved in sleep, temperature regulation,
thought, cognitive function, behaviour and mood, appetite, vomiting
and pain perception.
2. Precursor of melatonin :
5-HT is the precursor of melatonin in pineal gland.
It is believed to regulate the biological clock and maintain circadian
rhythm.
3. Neuroendocrine function :
It regulate anterior pituitary hormone.
Pathophysiological role

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4. Nausea and vomiting :
 Especially that evoked by cytotoxic drugs or radiotherapy
is mediated by release of 5-HT and its action on 5-HT3
receptors in the gut.
5. Migraine :
 initiate the vasoconstrictor phase of migraine and to participate in
neurogenic inflammation of the affected blood vessels.
6. Haemostasis :
Platelets release 5-HT during aggregation at the site of injury to
blood vessel.
5-HT accelerates platelet aggregation and clot formation.

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Synthesis inhibitor
• p-Chlorophenylalanine (PCPA) selectively inhibits tryptophan
hydroxylase (rate limiting step) and reduces 5-HT level in tissues. It is
not used clinically due to high toxicity.
Uptake inhibitor
• Tricyclic antidepressants inhibit 5-HT uptake along with that of NA.
The selective serotonin reuptake inhibitors (SSRI) like fluoxetine,
sertraline, etc. inhibit only 5-HT reuptake and have antidepressant
antianxiety property.
DRUGS AFFECTING 5-HT SYSTEM

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 18
Storage inhibitors
• Reserpine blocks 5-HT uptake into storage vesicles by inhibiting
VMAT-2, and causes depletion of all monoamines. Fenfluramine
selectively releases 5-HT by promoting its reverse transport at
serotonergic nerve endings in the brain, followed by its prolonged
depletion, and has anorectic property.
Degradation inhibitors
• Nonselective MAO inhibitor (tranylcypromine) and selective MAO-A
inhibitor (chlorgyline) increase 5-HT content by preventing its
degradation.

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5-HT receptor agonists
Azapirones like buspirone, gepirone and ipsapirone are a novel class
of antianxiety drugs which do not produce sedation. They act as
partial agonists of 5-HT1A receptors in the brain.
sumatriptan and other triptans are selective 5-HT1D/1B agonists,
constrict cerebral blood vessels and have emerged as the most
effective treatment of acute migraine attacks .
cisapride This prokinetic drug which increases gastrointestinal
motility is a selective 5-HT4 agonist. Renzapride is still more selective
for 5-HT4 receptors.

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 20
1.Cyproheptadine:
• H1 Receptor and 5-HT2A blocker.
• Has sedation and anticholinergic effect.
• Increases appetite.
• Useful in carcinoid and post gastrectomy dumping syndrome.
• Dry mouth, drowsiness, weight gain are some of the side effects.
2.ketanserin :
• 5-HT antagonist and a1-blocker.
• Has antihypertensive effect.
5-HT Antagonist

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 21
3.Ondansetron and Granisetron :
• They are 5-HT3 receptor antagonist.
• It control nausea and vomiting following administration of
highly emetic anticancer drugs and radiotherapy.
4.Atypical Antipsychotics:
• Clozapine, olanzapine, risperidone etc..,are 5-HT2 blockers
used in schizophrenia.
5. Methysergide :
• 5-HT2A/2C antagonist.
• It was used for prophylaxis of migraine.
• Long term use causes abdominal and pulmonary fibrosis.

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 22
Ergot alkaloids and their derivatives

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K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 23
• Cirillo C , Vanden Berghe P , Track J. Role of serotonin in
gastrointestinal physiology and pathology. Edizioni Minerva
Medica. 2011;36(4): 311-24.
• David A. Levy. Histamine and Serotonin. Springer.
2015;32:141-161.
• D.J David , A.M. Gardier. The pharmacological basis of
serotonin system: Application to antidepressant response.
Elsevier. 2016;42(3): 255-263.
References

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Thank you