1. AUTACOIDS (II)
5-Hydroxytryptamine
(5-HT)
SEROTONIN

2. • It is widely distributed in plants and
animals. Highest concentration in
mammals is found in the pineal gland,
acting as a precursor for melatonin. It
is synthesized from the amino acid
tryptophan and acts on several types of
receptors.

3. Sources:Platelets
Enterochromaffin cells (Intestines)
CNS:- Tryptaminergic Neurons

5. Physiological Functions
1. Neurotransmitter (CNS)
2. 5-HT released from platelets may account
for vasospasm that accompanies certain
diseases like Raynaud’s.
3. Regulation of intestinal activity.
4. Synthesis of Melatonin in Pineal body.

6. VASCULAR INJURY
5-HT2A
Accelerated
Platelet
Aggregation
Initial Platelet
aggregation
Release of 5-HT
5-HT1
Release of EDRF
(Vasodilatation)
5-HT2A
Thrombus
Heamostasis
Vascular occlusion
Vasoconstriction
5-HT
EFFECTS ON BLOOD VESSELS AND
HAEMOSTASIS

7. • 5-HT causes constriction of renal,
splanchnic, meningeal, and pulmonary
arteries and veins and venules, but
dilatation of the blood vessels of
skeletal musles, coronaries, and skin
capillaries. It has weak direct inochronotropic
effect
on
the
myocardium. It also stimulates smooth
muscles, especially of the intestines.

8. • Serotonin is widely distributed in the
CNS, serving as a neurotransmitter.
Altered functions may be responsible
for disturbances in sleep, mood, sexual
behavior,
motor
activity,
pain
perception, migraine, temperature
regulation,
endocrine
control,
psychiatric disorders and extrapyramidal activity.

9. PHARMACOLOGICAL ACTIONS
I. CARDIOVASCULAR SYSTEM
1. Blood Pressure
i.
Fall (Bezold Jarisch Reflex)
stimulation of sensory receptors in
heart.
ii.
Pressor phase:- Due to
vasoconstriction (Peripheral
vessels) and release of NE.

10. iii.
Prolonged Fall, with in 1 to 2
minutes of I/V injection.
Dilatation of B.V. in skeletal
muscles.

11. FALL
FALL
RISE

12. 2. Capillary Permeability:- Nil
3. Blood vessels and Hemostasis:- See Fig
4. Heart:- +ve Inotropic, +ve Chronotropic
II. SMOOTH MUSCLE
Bronchial and Intestinal smooth muscles
stimulated  Bronchospasm and Increased
peristalsis

13. III. Sensory neurons
5-HT receptors located on sensory neurons
mediate a depolarizing response causing:pain, itching, respiratory stimulation,
Bezold Jarisch reflex.

14. CARCINOID TUMOURS
Tumours of Enterochromaffin cells in G.I.T.
produce large quantities of 5-HT  Diarrhaea;
Bronchospasm; Edema; Vasodilatation &
Flushing; Release of Substance P; Formation of
Kinins.
Excessive utilization of Tryptophan 
Tryptophan Deficiency PELLAGRA

15. I. 5-HT AGONISTS
1. BUSPIRONE
Anxiolytic
2. TRIPTANS
i) Sumatriptan
ii) Naratriptan
iii) Rizatriptan
iv) Zolmitriptan
Treatment of Acute Migraine Headache
3. CISAPRIDE
Gastro Esophageal Reflux

16. Sumatriptan is a selective agonist of 5-HT1
receptors, highly effective in treating acute
attacks of migraine. It relieves the nausea and
vomiting, but the headache may recur,
necessitating repeated administrations.
• Adverse effects include flushing and heat at the
injection site, neck pain, dizziness, and tingling
of the hands.
• The drug is contraindicated with symptomatic
ischemic
heart
diseases,
angina,
and
hypertension as it may cause coronary
vasoconstriction.

17. II. 5-HT ANTAGONISTS
1. Ketanserin
Hypertension (α 1 blockade)
Vasospastic conditions
2. Methysergide (Sansert)
Prophylaxis of Migraine

18. 3. CYPROHEPTADINE (Periactin); also
blocks H1
Stimulation of appetite; Smooth muscle
manifestations of carcinoid tumours.
Post-gastrectomy dumping syndrome; Cold
induced urticaria.
4. CLOZAPINE
Antipsychotic (Schizophrenia)

19. 5. Risperidone (Blocks D2 also)
Schizophrenia
6. Ritanserin
Reduction of thromboxane formation
7. Ondansetron
Nausea and Vomiting associated with
cancer chemotherapy.

20. 8. Granisetron
As above
9. Alosetron
Irritable bowel syndrome.

21. SELECTIVE SEROTONIN
REUPTAKE INHIBITORS
CITALOPRAM
FLUOXETINE
FLUVOXAMINE
PAROXETINE
SERTRALINE

22. Very commonly used class of Antianxiety
and Antidepressant agents.
Like Tricyclic antidepressants, which
block NE uptake, the SSRIs block
neuronal transport of Serotonin.

23. Increased synaptic availability of Serotonin
stimulates a large number of Post-synaptic
5-HT receptor subtypes.
____________________________________
SIDE EFFECTS
•Nausea and Vomiting
•Risk of Agitation and Restlessness

24. RELEASE
REUPTAKE

25. Lysergic Acid
Diethylamide
(LSD)
TRYPTAMINERGI
C NEURON
Psychedelic
Sumatripta
Hallucinati
on
5-
Fluoxetine
5-
HT 2A
HT 1D
Antimigrain
e
Ondansetro
5-HT-retuptake
Inhibitor
Antidepressant
n
n
5-HT 3

27. QUESTIONS

28. 1. A patient has been diagnosed with a rare
metastatic carcinoid tumor. The neoplasm
is releasing serotonin, bradykinin and
several unknown peptides. The effects of
serotonin in this patient are most likely to
include which one of the following:
a)
b)
c)
d)
e)
Constipation
Episodes of bronchospasm
Hypotension
Hypersecretion of gastric acid
Urinary retention

29. 2. In recommending treatment for a patient
suffering from metastatic carcinoid tumors
the one least likely to be helpful is :
a)
b)
c)
d)
e)
Cyproheptadine
Ketanserin
Phenoxybenzamine
Sumatriptan
Ondansetron

30. 3. A patient undergoing cancer chemotherapy
is vomiting frequently. A drug that might
help in this situation is :
a)
b)
c)
d)
e)
Bromocriptine
Cimetidine
Ketanserin
Loratidine
Ondansetron

31. 4. Which of the following is a serotonin
agonist useful for aborting an acute
migraine headache and is not derived from
a fungus :
a)
b)
c)
d)
e)
Bromocriptine
Cimetidine
Ergotamine
Ketanserin
Sumatriptan