In a review of the literature of the serotonin toxidrome, the authors elegantly critiqued the diagnostic criteria and reviewed the mechanism and pathophysiology of toxicity. Of the seven serotonin receptors, which two receptors does excess serotonin act on to cause toxicity?
It is likely no single receptor is responsible for serotonin toxicity, but 5-HT1A and 5-HT2A have been implicated to cause serotonin toxicity. Agonism at the 5-HT1A receptors likely causes mild symptoms like anxiety and hyperactivity, because they have greater affinity for serotonin. The 5-HT2A receptors, with lower affinity for serotonin, become occupied when higher concentrations of serotonin exist in the synapse, which mediates severe serotonin toxicity.
Chiew AL, Buckley NA. The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes. Clinical Toxicology, 2022;60(2):143-158.
Contributed by: Kirk Cumpston, DO FAACT on behalf of The Medical Toxicology Fellowship, Virginia Commonwealth University