What is serotonin synthesized from?
What are the steps of synthesis and which is the rate limiting step (RLS)?
How is serotonin's action terminated?
Synthesized from Tryptophan
First step, tryptophan hydroxylase is RLS
Second step is L-aromatic amino acid decarboxylase: 5-HO-Tryptophan to 5-HT
Reuptake by SERT then converted 5-hydroxyindoleacetic acid via MAO and aldehyde DH
Conversion to melatonin in pineal gland
What is the location of serotonin in the body?
In the CNS specifically where is it?
90% - GI system
8% - Platelets (No synthesis)
2% - CNS
Cell bodies in midbrain raphe nuclei
Projection: Hypothalamus, neostriatum, limbic forebrain, neocortex, medulla, spinal cord
What are the serotonin receptors?
5-HT1(A-E) – Inhibition of adenylate cyclase
5-HT1A – K+ channel opens
5-HT2(A-C) – PI hydrolysis
5-HT3 – Ligand-gated cation channels
5-HT4-7 – Activation of adenylate cyclase or unknown
Auto-receptors – Decreased serotonin release (1A and 1D like)
What is the cardiovascular role of serotonin?
Potent vasoconstriction of large arteries and veins; cranial (5-HT1D) blood vessels
Vasodilation in coronary, skeletal muscle and cutaneous blood vessels
Bezold-Jarisch reflex – Coronary chemoreceptors; Bradycardia, hypotension, and hypoventilation
Platelet aggregation – Active uptake of serotonin from circulation
What is the CNS role of 5-HT
Learning and memory, particularly short-term
Pain perception – spinal and brain sites of action
Emesis – 5-HT3 receptors
What is the role of 5-HT in mental illness?
Affective disorders – SSRIs and SNRIs
Schizophrenia – Atypical antipsychotics
OCD – SSRIs
Anxiety – 5-HT1A receptors
Lysergic Acid Diethylamide (MoA, Indication)
Nonspecific – 5-HT2 receptors
Buspirone (MoA, Indication)
5-HT1A Partial Agonist – Antianxiety
Sumatriptan (Delivery, MoA, Indication)
Delivery: Oral, nasal spray, SC
Combination with naproxen
5-HT1B/D receptors on cerebral blood vessels (Vasoconstriction promoting)
CGRP – Inhibition of vasoactive peptides
NT inhibits of the trigeminal and cortical nerves
Block brainstem pain pathways
Treatment of migraine headaches, stop existing ones – Major abortive
Sumatriptan (Side Effects, Contraindications)
Nausea and vomiting
Uncontrolled HTN, IHD
Sumatripitan (Drugs in same class, and any details in delivery)
Almotriptan, eletriptan, frovatriptan (long half-life), naratriptan (long half-life), rizatriptan, zolmitripitan (oral, nasal spray)
What are some other abortives?
Ergots – DHE
Ergotamine – Oral
NSAIDS w/ caffeine (Excedrin)
Butalbital – Mild barbiturate
What are some prophylactic drugs for headache?
Tricyclic Antidepressents: Amitryptyline, Nortriptyline
Effective for variety of sources
Divalproex sodium/valproic acid
Others – Gabapentin, pregabalin, lamotrigine
Beta blockers – Propranolol, atenolol
Calcium channel blockers – Verapamil, diltiazem
Variable efficacy – Side effects