In serotonin anti-serotonin, kinin and prostaglandin autacoid we are learn all about Serotonin, its receptor, synthesis serotonin action on various body part, its uses, adverse effect, serotonin antagonist(anti-serotonin),all about kinin and prostaglandin

1. SEROTONIN
ANTISEROTONIN, KININ
AND PROSTAGLANDIN
AUTACOIDS
SUBJECT NAME: ADVANCE PHARMACOLOGY
GUIDED BY : Dr. D. S. SHIRODE
PRESENTED BY : ANKITA S. HALDANKAR
(M. Pharm 1st year Pharmacology)
D. Y. Patil College Of Pharmacy Akurdi, Pune

2. INTRODUCTION
• Serotonin ( 5 – Hydroxytryptamine) is a monoamine
Neurotransmitter.
• It has a popular image as a contributor to feeding of well being
and happiness.
• It is a important neurotransmitter widely distributed in
animals and plants (banana, pineapple,Tomato)
• 80-90% Found in enterochromafin cells in a gut where it is
used to regulate intestine movement, rest is present in platelet
and brain.
• Serotonin does not cross BBB necessitates the synthesis of
serotonin with in the brain.
• Serotonin is synthesized from the amino acid tryptophan
which derived from the diet.

4. RECEPTORS
Seven subtype of serotonin receptors(1-7)
Receptor Location
5HT1 CNS, Cranial blood vessel
5HT 2 Platelets, smooth muscles
5HT3 CTZ
5HT4 GIT, CNS
5HT 5-7 CNS
All of them are G – Protein coupled receptor except 5-HT 3( ligand
gated ion channel)
Drug acting on 5HT1A, 5HT1 B/D and 5HT 4 – Agonist
Drug acting on 5HT 2 A/C and 5HT 3 - Antagonist

5. 1.5HT 1A : anxiety
Drugs :Buspirone stimulate 5HT1A
Treatment :Anxiety (chronic anxiety)
2. 5HT 1B/D : Blood vessel of brain
Stimulant: Vasoconstriction
Treatment : Migraine
Drugs :(1) Sumatriptan (2) Naratriptan
3. 5HT 2A/C : Blood vessel – Vasoconstriction
Stimulant – Increase BP ( Vasoconstriction )
Drugs: Antagonist – kitaserin, Ritaserin
4. 5HT 3 : CTZ
Stimulant : Vomiting ( Cisplatin – maximum incidance of vomiting
)
Drug :Ondansetron, Granisetron
5. 5HT 4 : 1)Present in GIT
2) Increase forward movement of GIT

6. •CLASSIFICATION:

7. PHARMACOLOGICAL ACTION OF 5-HT
1)Heart : Bradycardia due to stimulation of coronary
chemoflex through vegus nerve.
2) Blood pressure : Triphasic response on BP
• Early sharp fall – Due to increase vagal activity
• Brief rise in BP – Due to Vasoconstriction
• Prolong fall in BP – Due to Arteriolar dilation
3) Gastrintestinal Tract :
• Increase gastric motility +contraction = Diarrhoea
• Activation of 5HT Receptor –Ach release –Prokinetic Effect
• PROKINETIC EFFECT : Any drug which increse the
forward movement of GIT

8. 4) Gland :
• 5HT Decrease gastric secretion result in decrese acid and
pepsin
• Increse mucus production – Ulcer protective effect
5) Nerve Ending :
• 5HT Activate Afferent nerve ending – Tingling And Pain
6) Platelet :
• 5HT 2 Promote platelet aggregation
7) CNS :
• Poor entry to BBB
• Direct injection in brain : hunger, behavioral changes,
sleepness

9. PATHOPHYSIOLOGICAL ROLE
1.Neurotransmitter :
• Action : Sleep, Temperature Regulation, mood stabilizer,
Pain, Cognitive function , Behavioural activity, Vomiting,
Thoughts, Appetite
2. Precursor of Melatonin :
• Precursor of melatonin at Pineal gland
• Maintain Circadian rhythm
3. Neuroendocrine function :Regulate anterior pitutary
hormone
4. Nausea and Vomiting :Cytotoxic drug and radiotherapy
receptor of gut 5HT 3
5. Migraine : Vasoconstrictor phase of Migraine –Sumatriptan

10. 5HT ANTAGONIST
1. Cyproheptadine:
• Block 5HT 2A receptor
• Utilized in Controlling Intestinal Manifestation of carcinoid & postgastrectomy
syndrome.
• Side effect : dry mouth, drowsiness, ataxia
2)Methylsergide :
• Antagonise the action of 5HT on smooth muscle including that of blood vessels.
• Used for migraine prophylaxis.
3) Resperidone :
• 5HT 2A antagonist.
• Produce extrapyramidal effect on slightly higher dose.
4)Ondansetron :
• Selectively 5HT3 antagonist.
• Remarkable efficacy in controlling nausea and vomiting following administration
of highly emetic anticancer drug & radiotherapy.

11. Kinins:
• Vasoactive polypeptide.
• Formed from plasma globulin kininogen.
• Enzyme involved Kallikrein.
• Generated by proteolytic reaction trigger by tissue
injury, inflammation, allergic reaction, etc
• Important kinin are:
1.Kallidin (decapeptide)
2.Bradykinin (nonapeptide)
Kinin Receptor
Two types of receptor
B1 receptor
B2 receptor ( kallidin & bradykinin)

12. 1.B1 receptor
• Mediate kinin action in inflamed tissue.
• Cause contraction of vein, large vessels,enhance prostaglandin
synthesis etc.
2.B2 receptor
• Mediate kinin action in non inflamed tissue.
• Cause visceral smooth muscle contraction.
Action of kinin:
1. Kidney:
• Increase renal blood flow.
• Facilitates watee and salt excretion.
2. Smooth muscle:
• Contraction of intestine
• Bronchoconstriction in guinepig and asthmatic patients.

13. 3. Neuron:
• Strongly stimulate nociceptive Afferent and produce burning sensetion.
• Bradykinin produce intense, transient pain so used in analgesic testing.
• Increase permeability of BBB.
4. Blood vessels :
• Potent vasodilator (via endothelial No and PGI 2 ) release.
• Increase capillary permeability due to separation of endothelial cell.
• No direct effect on heart; reflex stimulation due to fall in BP.
•PATHOPHYSIOLOGICAL ROLE OF KININS:
1.Mediation of inflammation.
2.Mediation of pain.
3.Major role in development of angioedema.
4. Hereditary angioedema

14. PROSTAGLANDIN
• Prostaglandin – product of long chain fatty acid.
• Prostaglandin are derivative of prostanoic acid.
• Prostaglandin are C20 prostanoic acid, 7( 2-octyl
cyclopentyl) heptanoic acid.
• Prostaglandin are differ in their structure due to
substituent group & double bond on cyclopentane ring.
• PG, LT, TX are collectively called as ecosonoid, and it is
synthesized from membrane phospholipid.

16. COX( Cyclooxygenase)
COX–1
• It is a constitutive enzyme (not inducible, always present in cell)
• Serve house keeping
• It participates in physiological functions such as secretion of mucus
for protection of gastric mucosa, haemostasis and maintainance of
renal function.
COX–2
• It is an inducible enzyme
• It involve in inflammatory & other pathological changes.
COX–3
• Involve in pain perception & fever but not in the inflammation.
• This isoenzyme is inhibited by paracetamol.

17. PHARMACOLOGICAL ACTION
1)Platelets:
• TXA2 – Potent aggregator of platelets.
• PGI2 – Inhibit platelet aggregation.
2) Blood vessels:
• PGI2 & PGE2 –Vasoconstriction
• TXA2 – Vasoconstriction
3) Uterus :
• PGE2,PGF2a – Constriction
• Dysmenorrhea – occur due to increase local production of PG by the endometrium.
4) Bronchi:
• PGE2>>PGI2 – Bronchodilation
• PGF2a, TXA2 – Bronchoconstriction
5) GIT
• Intestine – increase water, electrolyte, mucus secretion – diarrhoea.
• Stomach – (PGE2) – increase mucus and decrease HCL Secretion
6) EYE – (PGF2a)
• Decrease intraocular tension.

18. Preparation and uses of prostaglandin
1.PGE1 (Alprostadil)- Erectile dysfunction
2.PGE2 ( Gemeprost) – Cervical ripening in early
pregnancy
3.PGE2 ( Misoprostol) – Peptic ulcer, Abortion
4.PGE2 (Dinoprostone) – Induction of labour
5.PGF2a ( Dinoprostone)- Mild term abortion
6.PGF2a ( Latanoprost) – Glaucoma
7.PGI2 ( Epoprostenol) – Pulmonary hypertension