5 - HT / Serotonin

Question 1

What is serotonin synthesised from?

Answer 1

From tryptophan by tryptophan hydroxylase and an ubiquitous carboxylase.

Question 2

What does degradation of serotonin occur by?

Answer 2

Monoamine oxidase

Question 3

What does degradation by monoamine oxidase form?

Answer 3

5-hydroxyindoleacetic acid (5-HIAA)

Question 4

Where is endogenous 5-HT found?

Answer 4

Enterochromaffin cells & enteric nerves on wall of intestine: gastric peristalsis & emptying
Platelets: aggregation, haemostasis, alter local vascular supply
They get loaded with 5-HT as they pass through intestinal circulation where there is high concentration storage, release and uptake of 5-HTs
CNS: act as a neurotransmitter

Question 5

Effect of 5-HT on GIT

Answer 5

Gut peristalsis and secretion, gastric emptying

Question 6

Effect of 5-HT on platelets

Answer 6

Platelet aggregation

Question 7

What is the effect of 5-HT on blood vessels?

Answer 7

Vasodilation (eg. arterioles by causing endothelial cells to release NO & inhibit noradrenaline release)
Vasoconstriction (eg. large vessels)

Question 8

What is the effect of 5-HT on cardiac muscle?

Answer 8

Direct increase rate and force

Question 9

What is the effect of 5-HT on chemoreceptors?

Answer 9

Indirectly mediated bradycardia (vagus8) and vasodilation

Question 10

Receptor subtype of GIT for 5-HT?

Answer 10

5-HT2/5-HT3
5-HT4

Question 11

Receptor subtype of Platelets for 5-HT?

Answer 11

5-HT2

Question 12

Receptor subtype of blood vessels for 5-HT?

Answer 12

5-HT1
5-HT1/5-HT2

Question 13

Receptor subtype of cardiac muscle for 5-HT?

Answer 13

5-HT4

Question 14

Receptor subtype of chemoreceptors for 5-HT?

Answer 14

5-HT3

Question 15

Agonist of 5-HT1 ( decrease cAMP)

Answer 15

5-carboxamido tryptamine (5-CT) – vasoconstriction

Question 16

Antagonist of 5-HT1

Answer 16

Ergotamine (PA) – ergot alkaloid drug with anti-migraine effect due to constriction of the intracranial extra-cerebral blood vessels

Question 17

Agonist of 5-HT(1A)

Answer 17

Buspirone (PA) - treat GAD

Question 18

Antagonist of 5-HT(1A)

Answer 18

Methysergide (PA)

Question 19

Agonist of 5-HT(1B) and 5-HT(1D) and effect

Answer 19

Sumatriptan – reduces vascular inflammation associated with migraine

Question 20

Agonist of 5-HT(1F) and effect

Answer 20

Lasmiditan – investigational drug for treatment of acute migrane, might have fewer side-effects compared to triptans

Question 21

Agonist of 5-HT2A-C (↑ IP3) and effect

Answer 21

α-methyl 5-HT (αMS) – acts on 5-HT2 to cause vasodilation, has longer half-life as not metabolized by MOA and no CNS effects as –OH group reduces its ability to cross BBB.
LSD – psychedelic drug

Question 22

Antagonist of 5-HT2A-C (↑ IP3) and effect

Answer 22

Methysergide (PA) – prophylactic but no longer recommended due to retroperitoneal fibrosis.

Question 23

Agonist of 5-HT2C (mostly in brain) and effect

Answer 23

Lorcaserin – weight-loss drug with CNS effects

Question 24

Agonist of 5-HT3 and effect

Answer 24

2-methyl 5-HT

Question 25

Antagonist of 5-HT2C (mostly in brain) and effect?

Answer 25

Pizotifen – preventative drug to reduce frequency of recurrent migraine Acts on 5-HT2A as well

Question 26

Antagonist of 5-HT3 (channel) and effect

Answer 26

Ondansetron & Tropisetron – antiemetic drugs, particularly for controlling severe nausea & vomiting that occurs with many forms of cancer chemotherapy.

Question 27

Agonist of 5-HT4 (↑ cAMP) and effect

Answer 27

5-methoxytryptamine (5-MT) – cardiac stimulant effects Tegaserod – promote gastric emptying/alter peristalsis, increase colon activity

Question 28

Antagonist of 5-HT4 (↑ cAMP) and effect

Answer 28

Tropisetron blocks this receptor as well

Question 29

Ergotism defn

Answer 29

The effect of long-term ergot poisoning, traditionally due to the ingestion of the alkaloids produced by the Claviceps purpurea fungus that infects rye and other cereals.

Question 30

NANC receptor peptides

Answer 30

- Kinins - Angiotensin II - Endothelins

Question 31

Kinins effects (2)

Answer 31

B1: arterial (vein) constrict B2: arteriolar (venule) dilation (NO) – increase capillary permeability

Question 32

Angiotensin effects (2)

Answer 32

AT1: arteriolar constriction, aldosterone release AT2: catecholamine release

Question 33

Endothelins

Answer 33

ET(A) & ET(B) (Bosentan is a competitive ET antagonist used in the treatment of pulmonary artery hypertension (PAH), by constricting pulmonary blood vessels)

Question 34

Other NANC receptor peptides (3)

Answer 34

Y1-6 receptors: Neuropeptide Y (NPY) VPAC1,2 receptors: Vasoactive intestinal polypeptide (VIP) Neurokinin receptors, NK1-3: Substance P