Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness. The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets. Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock. It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.

1. DR. CHAVAN P. R.
PHARM D
Seretonin and Its Antagonists

2. Introduction
5-hydroxytryptamine (5-HT)
 Seretonin - vasoconstrictor substance which
appeared in the serum when blood clotted
 Enteramine - smooth muscle contracting substance
present in enterochromaffin cells of gut mucosa
Sources – intestines (90%), platelets and brain, wasp
and scorpion sting, invertebrates and plants
(banana, pear, pineapple, tomato, stinging nettle,
cowhage).

4. Receptors

5. Pharmacological actions
CVS
 Larger arteries and veins are characteristically constricted,
 In the microcirculation 5-HT dilates arterioles and
constricts venules, capillary pressure rises and fluid escapes.
 BP: Triphasic response with 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.

6. Visceral smooth muscles
 Potent stimulation of G.i.t. and constriction of
bronchi
Glands
 Inhibits gastric secretion (both acid and pepsin), but
increases mucus production and has ulcer protective
property

7. Nerve endings and adrenal medulla
 Afferent nerve endings are activated causing tingling
and pricking sensation, as well as pain.
 Depolarization of visceral afferents elicits respiratory
and cardiovascular reflexes, nausea and vomiting
Respiration
 Brief stimulation of respiration and hyperventilation
are the usual response

8. Platelets
 Weak Platelets aggregator
CNS
 Poor entry across blood brain barrier
 Direct injection in the brain produces sleepiness,
changes in body temperature, hunger and a variety
of behavioural effects.

9. Pathophysiologic role
1. Neurotransmitter
2. Precursor of melatonin
3. Neuroendocrine function
4. Nausea and vomiting
5. Migraine
6. Haemostasis
7. Raynaud’s phenomenon
8. Variant angina
9. Hypertension
10. Intestinal motility
11. Carcinoid syndrome

10. DRUGS AFFECTING 5-HT SYSTEM
5-HT PRECURSORS
 Tryptophan increase brain 5-HT & produce behavioral
effects.
SYNTHESIS INHIBITORS
 p-Chlorophenylalanin selectively inhibit tryptophan
hydroxylase & reduce 5-HT level in tissue.
UPTAKE INHIBITORS
 Tricyclic antidepressants inhibit 5-HT uptake along with
NA .Some like fluoxetine ,sertraline are selective
serotonin reuptake inhibitors.

11. STORAGE INHIBITORS
 Reserpine block 5-HT uptake into storage granules &
cause depletion of all cell monoamines .
DEGRADATION INHIBITORAS
 Non-selective MAO inhibitors (tranylcypromine) &
selective MAO –A inhibitors (chlorgyline) increase 5-HT
content by preventing its degradation.
NEURONAL DEGENRATION
 5,6 Dihydroxytryptamine selectively destroys 5-HT
neurons .

12. 5-HT RECEPTOR AGONISTS
D-Lysergic acid diethyl amide(LSD)
 Non selective 5-HT agonist
 Activates subtypes of 5-HT receptors including 5-HT1A,
5HT2A/2C ,5HT5-7
 Antagonize 5HT2A receptor in ileum
AZAPIRONES
 Like buspirons ,gepirone act as partial agonist of 5HT1A
Receptor in brain.
8 HYDROXYDIPROPYLAMINO TETRALINE
 Selective 5HT1A agonist
 Used as experimental tool

13. SUMATRIPTAN AND OTHER TRIPTAN
 Selective 5HT1B/1D agonists
 Most effective in treatment of acute migraine attack
CISAPRIDE
 Prokinetic drug
 increase g.i.t motility
 Selective 5HT4 agonist
 M-Cholorophenylpiperazine
 Active metabolite of antidepressant drug
TRAZODONE
 found to be agonist of 5HT1B 5HT2A/2C Receptor in brain.

14. 5-HT RECEPTOR ANTAGONISTS
 Cyproheptadine
 Methysergide
 Ketanserin
 Clozapine
 Risperidone
 Ondansetron

15. CYPROHEPTADINE
 Block 5HT2A receptor
 Utilized in controlling intestinal manifestations of
carcinoid & postgastrectomy dumping syndrome
 Antagonize priapism caused by 5HT uptake inhibitor
like fluoxetine
 Side effects: Drowsiness, Dry Mouth , Ataxia
Confusion.

16. METHYSERGIDE
 Antagonize action of 5HT on smooth muscles
including that of blood vessels
 Potent 5HT2A/2C ANTAGONIST & Non selectively
act on 5HT1 receptors
 Used for migraine prophylaxis

17. RISPERIDONE
 5HT2A antagonist
 Ameliorates negative symptoms of schipherenia
 Produce extrapyramidal side effects on slightly
higher doses

18. ONDANSETRON
 Selectively 5HT3 Antagonist
 Remarkable efficacy in controlling nausea &
vomiting following administration of highly emetic
anticancer drugs & radiotherapy .

19. KETANSERIN
 Selective 5HT2 receptor blocking property with
action on 5HT1,5HT3 & 5HT4 receptors .
 5HT induced vasoconstriction ,platelets aggregation
& contraction of airway smooth muscles are
antagonized but not contraction of guinea pig ileum
or rat stomach .

20. CLOZAPINE
 5HT2A/2C blocker
 Inverse agonist activity at cerebral 5HT2A/2C
Receptors
 Efficacy in resistant cases of schizophrenia

21. Thank You