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Pathway Description
Amitriptyline Serotonin Antagonist Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-08-03
Last Updated: 2023-11-27
Amitriptyline is a tricyclic antidepressant indicated in the treatment of depressive illness, either endogenous or psychotic, and to relieve depression associated anxiety. The non-FDA-approved indications are anxiety, post-traumatic stress disorder, insomnia, chronic pain (diabetic neuropathy, fibromyalgia), irritable bowel syndrome, interstitial cystitis (bladder pain syndrome), migraine prophylaxis, postherpetic neuralgia, and sialorrhea. The three-ring central structure, along with a side chain, is the basic structure of tricyclic antidepressants.
The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects. Amitriptyline by blocking the reuptake of both serotonin and norepinephrine neurotransmitters. In serotonergic neurons, serotonin is synthesized from tryptophan and stored in synaptic vesicles. Once an action potential arrives at the nerve terminal, calcium channels open, causing the influx of calcium in the cytosol. Calcium then triggers the release of neurotransmitters stored in synaptic vesicles via exocytosis. The serotonin is released into the synapse and acts on 5HT2A and 5HT2C receptors which are responsible for mood improvements. The serotonin in the synapse is rapidly taken up by the serotonin reuptake transporter on the presynaptic neuron, and is recycled. Amitriptyline inhibits these reuptake transporters on serotonergic neurons, thereby increasing serotonin concentration in the synapse. This allows more stimulation of 5HT2A and 5HT2C receptors needed to improve depressive moods.
References
Amitriptyline Serotonin Antagonist Pathway References
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