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Pharmacology Block 2 > 07 Serotonin > Flashcards

07 Serotonin Flashcards

1
Q

What essential amino acid is serotonin synthesized from?

A

Tryptophan

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2
Q

The rate-limiting enzyme in serotonin synthesis is?

A

Tryptophan Hydroxylase

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3
Q

Is tryptophan hydroxylase rate-limiting in synthesis of serotonin in CNS?

A

Not rate-limiting because of low tryptophan levels

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4
Q

What co-factors are required for serotonin synthesis?

A

O2 and reduced pteridine cofactor

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5
Q

What enzyme is involved in synthesis of catecholamines like serotonin?

A

L-aromatic amino acid decarboxylase

Uses pyridoxine cofactor

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6
Q

What is serotonin converted into in the pineal gland?

A

Melatonin

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7
Q

How is serotonin metabolized?

A

Neuronal action terminated primarily by high affinity active reuptake mechanism (SERT) and then intraneuronal conversion by monoamine oxidase (MAO) and aldehyde dehydrogenase to 5- hydroxyindole acetic acid

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8
Q

Where is the majority of serotonin distributed?

A

90%– Enterochromaffin cells of GI mucosa

    • synthesis and storage
    • slow spontaneous release (1 day)
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9
Q

Of the locations serotonin is distributed, where is it not synthesized?

A

Blood platelets

    • stored in vesicles with ATP
    • no synthesis
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10
Q

Where is serotonin located in the CNS?

A

Cell bodides in midbrain raphe nuclei (2%)

– project to hypothalamus, neostriatum, limbic forebrain, neocortex, medulla, and spinal cord

    • synthesis, storage, and release
    • rapid turn over (<4 hours)
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11
Q

Of the serotonin receptors, which is NOT a GPCR?

A

5-HT3 – ligand-gated Cation channel

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12
Q

What is the effector pathway of 5-HT1(A-E)?

A

Inhibition of adenylate cyclase

HT1A also opens K+ channels

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13
Q

What is the effector pathway of 5-HT2(A-C)?

A

Phosphoinositide hydrolysis

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14
Q

What is the effector pathway of 5-HT3?

A

Ligand-gated cation channel

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15
Q

What is the effector pathway of 5-HT4-7?

A

Activation of adenylate cyclase

5-HT5B unknown

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16
Q

What is the function of serotonin auto-receptors and what receptors are they like?

A

Decrease serotonin release

Like 5-HT1A and 5-HT1D

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17
Q

What serotonin receptor results in the inhibition of adenylate cyclase?

A

5-HT1(A-E)

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18
Q

What serotonin receptor results in phosphoinositide hydrolysis?

A

5-HT2(A-C)

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19
Q

What serotonin receptor is a ligand-gated cation channel?

A

5-HT3

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20
Q

What serotonin receptor activates adenylate cyclase?

A

5HT4-7

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21
Q

What is the function of serotonin the in GI system?

A

Causes contraction of G.I. smooth muscle including esophagus, stomach and intestine, increasing tone, peristalsis, and diarrhea

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22
Q

What receptor induces emesis?

A

5-HT3 in GI tract and brain

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23
Q

What is the carcinoid syndrome?

A

Serotonin secreting tumors and bradykinin of enterochromaffin cells

– cause severe diarrhea and asthma

Tx: 5-HT antagonist or somatostatin analog that blocks the secretion of all mediators from tumor

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24
Q

What is the effect of serotonin on large arteries and veins in most vascular beds and cranial blood vessels?

A

Potent vasoconstriction

25
What is the effect of serotonin on smooth muscle cells and the brain?
Vasoconstriction
26
What serotonin receptors are found on smooth muscle cells?
5-HT2 receptors
27
What serotonin receptors are found in the brain?
5-HT1D
28
What is the Bezold-Jarish reflex and what is activated by serotonin?
Serotonin is a powerful activator of chemoreceptors in coronary vasculature which activates afferent vagal nerve endings. The response is bradycardia, hypotension and hypoventilation.
29
What is the effect of serotonin on chemoreceptors in coronary vasculature?
Activation! Bezold-Jarish reflex: Bradycardia, hypotension, and hypoventilation
30
What is the effect of serotonin on platelets?
Active uptake of serotonin from circulation results in platelet aggregation
31
As a neurotransmitter, serotonin may be involved in what functions/perceptions/regulations?
- sensory perception (LSD) - sleep - temperature regulation - neuroendocrine regulation (release ACTH, GH, prolactin, TSH, FSH and LH) - learning and (short-term) memory - pain perception - drug abuse - emesis (5-HT3 receptors) - Mental Illness: - Affective disorders - Schizophrenia - Obsessive-compulsive disorder - Anxiety disorders (5-HT1A receptors) - Aggressive behavior
32
What types of drugs treat affective disorders?
Serotonin Specific Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake inhibitors (SNRIs)
33
What types of drugs treat schizophrenia?
Atypical antipsychotics
34
What types of drugs treat obsessive-compulsive disorder?
Serotonin Specific Reuptake Inhibitors (SSRIs)
35
Activation of what serotonin receptor results in anxiety?
5-HT1A
36
Lysergic Acid Diethylamide
Serotonin Agonist Full or partial agonist at 5-HT2 receptors -- Potent hallucinogen
37
What drug is a full or partial agonist at 5-HT2 receptors and is a potent hallucinogen?
Lysergic Acid Diethylamide
38
Buspirone
Serotonin Agonist Partial agonist at 5-HT1A receptors Tx: Anti-anxiety
39
What drug is a partial agonist at 5-HT1A and is an antianxiety agent?
Buspirone
40
Sumatriptan
Serotonin Agonist - - 5-HT1D receptors on cerebral blood vessels - - inhibit release of vasoactive peptides-- Calcitonin gene related peptide (CGRP) - - promote vasoconstriction Tx: migraine headaches Side effects: n/v, angina, dizziness and flushing
41
What drug binds 5-HT1D on cerebral blood vessels to treat migraine headaches?
Sumatriptan
42
Fluoxetine
Indirect Serotonin Agonist Serotonin specific Reuptake Inhibitor - blocks active reuptake of serotonin into neurons-- increases amount of serotonin at synapse Tx: affective disorders, obsessive-compulsive disorders, panic attacks, etc.
43
What drug blocks the active reuptake of serotonin?
Fluoxetine Serotonin Specific Reuptake Inhibitors (SSRIs)
44
What do SSRIs treat?
Ex. Fluoxetine Tx: affective disorders, obsessive-compulsive disorders, panic attacks, etc.
45
Phenelzine
Indirect Serotonin Agonist Monoamine Oxidase Inhibitors -- block metabolism of serotonin, NE, and DA Tx: affective disorders and narcolepsy Side effect: hypertensive crisis
46
What do monoamine oxidase inhibitors block?
Black metabolism of serotonin, NE, and DA
47
What indirect serotonin agonist can result in a side effect of hypertensive crisis?
Phenelzine
48
What drug can be used to treat narcolepsy and affective disorders?
Phenelzine
49
Cyproheptadine
Serotonin Antagonist - 5-HT2 receptor antagonist; H1 antagonist Tx: skin allergies, pruritus, and urticaria. Tx of carcinoid
50
What drug is a 5-HT2 receptor antagonist?
Cyproheptadine
51
What drug is used in treatment of skin allergies like pruritus and utricaria as well as carcinoid?
Cyproheptadine
52
Ondansetron
Serotonin antagonist - 5-HT3 receptor antagonist - acts at both GI and brain receptors Tx: chemotherapy induced n/v
53
What drug is used to treat chemotherapy induced n/v?
Ondansetron
54
What drug works on both 5-HT3 receptors of the CNS and GI?
Ondansetron
55
Alosetron
Serotonin Antagonist - selective 5-HT3 antagonist Tx: diarrhea predominantly from IBS in women AEs: severe GI - Restricted in women
56
What drug is a selective 5-HT3 antagonist?
Alosetron
57
What drug is used to treat diarrhea predominantly from IBS in women?
Alosetron
58
What drug is a target for insomnia treatment because it entrains the circadian clock?
Melatonin

Pharmacology Block 2 (12 decks)

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