Serotonin Receptors & Migraines

What drug classes are used for acute migraine treatment?

- Triptans

- Lasmiditan

- Ergots

- NSAIDs

- Gepants

- Antiemetics

What drug classes are used for migraine prevention?

- Beta blockers

- Anticonvulsants

- TCA antidepressants

- Onabotulinum toxin

- Monoclonal antibodies against CGRP

What is serotonin derived from?

Tryptophan

What does serotonin do in the periphery?

- Induces blood platelet aggregation

- Stimulates GI smooth muscle movement

- Stimulates pain and itch sensory nerve endings

- Induces contraction of vascular smooth muscle

- Causes vasodilation in skeletal and heart muscle

Where are cell bodies of serotonin neurons located?

Midbrain raphe nucleus

What does serotonin do in the brain?

- Sleep/arousal

- Mood/emotion

- Appetite

- Body temperature

What serotonin receptors are Gi/o-coupled (decrease cAMP)?

- 5HT1A

- 5HT1B

- 5HT1D

- 5HT1F

What serotonin receptors are Gq-coupled (increase calcium)?

- 5HT2A

- 5HT2B

- 5HT2C

What serotonin receptor is a ligand-gated cation channel?

5HT3

What serotonin receptors are Gs-coupled (increase cAMP)?

- 5HT4

- 5HT5

- 5HT6

- 5HT7

How does buspirone work?

- Partial agonist

- Targets 5HT1A

- Treats anxiety

- Decreases cAMP

How do triptans work?

- Targets 5HT1B

- Targets 5HT1D

- Decreases cAMP

- Treats migraines

- Agonist

How does lasmiditan work?

- Targets 5HT1F

- Decreases cAMP

- Agonist

- Treats migraines

How do risperidone and olanzapine work?

- Targets 5HT2A

- Targets 5HT2C

- Increases calcium

- Antagonist

- Treats schizophrenia

How does LSD work?

- Targets 5HT2A

- Targets 5HT2C

- Increases calcium

- Agonist

How does ondansetron work?

- Targets 5HT3

- Antagonist

- Treats chemotherapy-induced emesis

What is the first-line treatment to treat acute migraines?

Triptans

Activation of which type of serotonin receptors leads to decreased cyclic AMP in cells?

5-HT 1D

What is SERT?

- Serotonin transporter

- Located on the presynaptic terminals of serotonin neurons

- Target of antidepressants and psychostimulants

What causes the migraine aura?

Cortical spreading depression

What causes migraine pain?

- Activation of trigeminal system

- Vasoactive neuropeptides (CGRP)

What drugs are used as adjuvants for acute treatment of mild to moderate migraines?

- Naproxen

- Caffeine

- Metoclopramide

How does caffeine work as an adjuvant for acute treatment of mild to moderate migraines?

- Cerebral vasoconstriction

- Can potentiate analgesics

How does metoclopramide work as an adjuvant for acute treatment of mild to moderate migraines?

- Agonist at D2 receptor

- Anti-emetic

- Enhances gastric emptying

What are the treatment options for acute treatment of severe migraines?

- Triptams

- Ergots

- Lasmiditan

- CGRP receptor blockers

How do ergots work for migraines?

Non-selective 5HT receptor agonists

What are the ergots used for acute treatment of severe migraines?

- Ergotamine

- DHE (dihydroergotamine)

What are the CGRP receptor blockers used for acute treatment of severe migraines?

- Ubrogepant

- Rimegepant

What drugs are in Treximent?

- Sumatriptan

- Naproxen

Which triptans are available as nasal sprays?

- Sumatriptan

- Zolmitriptan

Which triptan is available as a powder?

Sumatriptan

What are the main side effects of triptans?

- Coronary artery vasoconstriction

- Serotonin syndrome

What should not be used while on a triptan?

- MAOIs

- Serotonin reuptake inhibitors

- Certain herbal supplements (St. John's wort)

What are the symptoms of serotonin syndrome?

- Autonomic instability (tachycardia, hyperthermia)

- N/V/D

- Muscle hyper-reflexia

- Incoordination

- Agitation

- Hallucinations

What are the side effects of lasmiditan?

- Dizziness

- Fatigue

- Paresthesia

- Serotonin syndrome

- Sedation

What are the key points of lasmiditan?

- Not for migraine prevention

- Treats acute migraines, not first-line

What ergot comes as a nasal spray for acute migraines?

DHE (dihydroergotamine)

What are the side effects of ergots?

- Nausea/vomiting

- Dizziness

- Cramps

- Vertigo

- Prolonged vasospasm causing angina/gangrene

After how long does ergotamine dependence occur?

> 3 weeks

In what patients are ergots contraindicated?

- Pregnancy

- Sepsis

- Vascular diseases

With what drug classes do ergots interact?

- Triptans

- Beta blockers

- Nicotine

What is the main reason that ergots are contraindicated in pregnancy?

Ergots induce smooth muscle contraction in the uterus

What are the CRGPs that treat migraines in adults?

- Ubrogepant

- Rimegepant

- Zavegepant

What CRGPs are used for preventative treatment of episodic migraines in adults?

- Atogepant

- Erenumab

- Galcanezumab

- Fremanezumab

- Eptinezumab

In what dosage form is ubrogepant available?

Oral tablet

In what dosage form is rimegepant available?

ODT

In what dosage form is zavegepant available?

Nasal spray

In what dosage form is atogepant available?

Oral tablet

In what dosage form is erenumab available?

SC autoinjector

In what dosage form is galcanezumab available?

SC injection pen

In what dosage form is fremanezumab available?

SC injection

In what dosage form is eptinezumab available?

IV injection

What are the beta blockers used to prevent migraines?

- Propranolol

- Timolol

What are the anticonvulsants used to prevent migraines?

- Valproate

- Topiramate

What is the antidepressant used to prevent migraines?

Amitriptyline