[AUTACOIDS] Serotonin

● Small intestine (enterochromaffin cells)

● Platelets

● GIT

● CNS (brain)

[BIOSYNTHESIS]

Serotonin is found in:

small intestine (enterochromaffin cells)

[BIOSYNTHESIS]

Serotonin is found in the_______ which manufacture >90% of serotonin.

tryptophan

[BIOSYNTHESIS]

Serotonin (5-HT) is synthesized from ____ through a two-step enzymatic process.

First, tryptophan is converted to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase (rate-limiting step).

Then, 5-HTP undergoes decarboxylation by aromatic L-amino acid decarboxylase to produce serotonin (5-hydroxytryptamine or 5-HT).

tryptophan hydroxylase

[BIOSYNTHESIS]

Serotonin (5-HT) is synthesized from tryptophan through a two-step enzymatic process.

First, tryptophan is converted to 5-hydroxytryptophan (5-HTP) by the enzyme ______ (rate-limiting step).

Then, 5-HTP undergoes decarboxylation by aromatic L-amino acid decarboxylase to produce serotonin (5-hydroxytryptamine or 5-HT).

decarboxylation

[BIOSYNTHESIS]

Serotonin (5-HT) is synthesized from tryptophan through a two-step enzymatic process.

First, tryptophan is converted to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase (rate-limiting step).

Then, 5-HTP undergoes ______ by aromatic L-amino acid decarboxylase to produce serotonin (5-hydroxytryptamine or 5-HT).

L-amino acid decarboxylase

[BIOSYNTHESIS]

Serotonin (5-HT) is synthesized from tryptophan through a two-step enzymatic process.

First, tryptophan is converted to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase (rate-limiting step).

Then, 5-HTP undergoes decarboxylation by aromatic ______ to produce serotonin (5-hydroxytryptamine or 5-HT).

CNS (presynaptic)

[EFFECTS OF SEROTONIN]

Location of 5-HT1A

CNS (presynaptic) → inhibit further release

[EFFECTS OF SEROTONIN]

Effects of 5-HT1A

Cerebral blood vessel

[EFFECTS OF SEROTONIN]

Location of 5-HT1B/1D

Cerebral vasoconstriction

[EFFECTS OF SEROTONIN]

Effects of 5-HT1B/1D

● Smooth muscles

- Uterus

- Cerebral blood vessels

- Bronchi

- Platelets

[EFFECTS OF SEROTONIN]

Location of 5-HT2A/2B

● Uterus → Oxytocic

● Cerebral blood vessels → Vasoconstriction

● Bronchi → Bronchoconstriction

● Platelets → Aggregation (clot)

[EFFECTS OF SEROTONIN]

Effects of 5-HT2A/2B

Chemoreceptor Trigger Zone

[EFFECTS OF SEROTONIN]

Location of 5-HT3

Chemoreceptor Trigger Zone → Emesis

[EFFECTS OF SEROTONIN]

Effects of 5-HT3

GIT

[EFFECTS OF SEROTONIN]

Location of 5-HT4

GIT → Peristalsis

[EFFECTS OF SEROTONIN]

Effects of 5-HT4

● PARTIAL agonist

- Buspirone

- Cisapride

- Tegaserod

● FULL agonist

- Triptans (sumatriptan, noratriptan, zolmitriptan)

- Prucalopride

[DRUGS FOR SEROTONIN]

Serotonin AGONISTS include:

● Buspirone (5-HT1A)

● Cisapride (5-HT4)

● Tegaserod (5-HT4)

[DRUGS FOR SEROTONIN]

Serotonin PARTIAL AGONISTS include:

● Triptans (sumatriptan, noratriptan, zolmitriptan) → 5-HT1B/1D

● Prucalopride (5-HT4)

[DRUGS FOR SEROTONIN]

Serotonin FULL AGONISTS include:

5-HT1A

[DRUGS FOR SEROTONIN]

Receptor of Buspirone

Anxiolytics

[DRUGS FOR SEROTONIN]

Use of Buspirone

5-HT1B/1D

[DRUGS FOR SEROTONIN]

Receptor of Triptans (sumatriptan, noratriptan, zolmitriptan)

Antimigraine

[DRUGS FOR SEROTONIN]

Uses of Triptans (sumatriptan, noratriptan, zolmitriptan)

5-HT4

[DRUGS FOR SEROTONIN]

Receptor of Cisapride, Tegaserod

Management of Irritable Bowel Syndrome (CONSTIPATION)

[DRUGS FOR SEROTONIN]

Uses of Cisapride, Tegaserod

5-HT4

[DRUGS FOR SEROTONIN]

Receptor of Prucalopride

Management of Irritable Bowel Syndrome (CONSTIPATION)

[DRUGS FOR SEROTONIN]

Uses of Prucalopride

● Cyproheptadine

● Setrons (ondansetron, granisetron, palonosetron, alosetron)

● Ketanserin

[DRUGS FOR SEROTONIN]

Serotonin ANTAGONISTS include:

5-HT1/2

[DRUGS FOR SEROTONIN]

Receptor of Cyproheptadine

Serotonin syndrome

[DRUGS FOR SEROTONIN]

Use of Cyproheptadine

5-HT3

[DRUGS FOR SEROTONIN]

Receptor of Setrons (ondansetron, granisetron, palonosetron, alosetron)

Antiemetics in cancer chemotherapy

[DRUGS FOR SEROTONIN]

Use of Setrons (ondansetron, granisetron, palonosetron, alosetron)

Alosetron

[DRUGS FOR SEROTONIN]

This is used for IBS (DIARRHEA) alosetron

5-HT 2A/2B

[DRUGS FOR SEROTONIN]

Receptor of Ketanserin

Antihypertensive

[DRUGS FOR SEROTONIN]

Use of Ketanserin

Claviceps purpurea

[DRUGS FOR SEROTONIN]

Ergots are derived from:

● Alpha-1

● Dopamine

● 5-HT2 (mixed agonist and antagonist)

[DRUGS FOR SEROTONIN]

Target receptors of ergots:

● Ergotamine

● Ergonovine

[DRUGS FOR SEROTONIN]

Ergots that are 5HT2 AGONIST include:

Ergotamine

[DRUGS FOR SEROTONIN]

This ergot 5HT2 agonist is VASOSELECTIVE, used as ANTIMIGRAINE.

Ergonovine

[DRUGS FOR SEROTONIN]

This ergot 5HT2 agonist is UTEROSELECTIVE, used in POST PARTUM BLEEDING and ANTI-MIGRAINE.

Methysergide

[DRUGS FOR SEROTONIN]

Ergots that are 5HT2 ANTAGONIST include:

Methysergide

[DRUGS FOR SEROTONIN]

This ergot 5HT2 antagonist is used in the PROPHYLAXIS of MIGRAINE HEADACHE.

● Gastrointestinal (GI) disturbances (more common)

● Vasospasm → gangrene (most serious)

● Retroperitoneal fibrosis (unique)

[DRUGS FOR SEROTONIN]

Toxic effects of ergots:

Gastrointestinal (GI) disturbances

[DRUGS FOR SEROTONIN]

MOST COMMON toxic effect of ergots:

Vasospasm → gangrene

[DRUGS FOR SEROTONIN]

MOST SERIOUS toxic effect of ergots:

Retroperitoneal fibrosis

[DRUGS FOR SEROTONIN]

MOST UNIQUE toxic effect of ergots: