Designing an Amitriptyline Derivative for Migraines with Minimal Cardiac Side Effects by Minimizing Binding Affinity to the Histamine H1 Receptor
School Name
South Carolina Governor's School for Science and Mathematics
Grade Level
12th Grade
Presentation Topic
Biochemistry
Presentation Type
Mentored
Abstract
Amitriptyline is a tricyclic antidepressant and is generally used to treat major depressive disorder, neuropathic pain, fibromyalgia, tension headaches, and migraines. Amitriptyline is effective for the treatment of migraines, but it has many adverse side effects, specifically cardiac side effects, such as prolonged QT interval, heart palpitations, and orthostatic hypotension. These side effects could be detrimental for a patient with POTS (Postural Orthostatic Tachycardia Syndrome), specifically hypovolemic POTS, which is characterized by chronically low levels of blood. The adverse side effects would have to be minimized before patients with cardiac issues could safely take this medication. Amitriptyline antagonizes the serotonin receptors 5-HT1A and 5-HT2A, which gives the medicine its migraine-relieving properties. The adverse side effects of amitriptyline, which are caused by antagonism of the Histamine H1 receptor, can be lessened by modifying the drug to not bind as well to H1. After many modifications of amitriptyline, I was able to create a successful compound that increased the affinity to 5-HT1A and 5-HT2A, as well as decreased the affinity to H1. These properties would make the medication more usable for a person with a comorbidity of POTS and migraines.
Recommended Citation
Byrd, Lily, "Designing an Amitriptyline Derivative for Migraines with Minimal Cardiac Side Effects by Minimizing Binding Affinity to the Histamine H1 Receptor" (2024). South Carolina Junior Academy of Science. 436.
https://scholarexchange.furman.edu/scjas/2024/all/436
Location
RITA 363
Start Date
3-23-2024 9:30 AM
Presentation Format
Oral Only
Group Project
No
Designing an Amitriptyline Derivative for Migraines with Minimal Cardiac Side Effects by Minimizing Binding Affinity to the Histamine H1 Receptor
RITA 363
Amitriptyline is a tricyclic antidepressant and is generally used to treat major depressive disorder, neuropathic pain, fibromyalgia, tension headaches, and migraines. Amitriptyline is effective for the treatment of migraines, but it has many adverse side effects, specifically cardiac side effects, such as prolonged QT interval, heart palpitations, and orthostatic hypotension. These side effects could be detrimental for a patient with POTS (Postural Orthostatic Tachycardia Syndrome), specifically hypovolemic POTS, which is characterized by chronically low levels of blood. The adverse side effects would have to be minimized before patients with cardiac issues could safely take this medication. Amitriptyline antagonizes the serotonin receptors 5-HT1A and 5-HT2A, which gives the medicine its migraine-relieving properties. The adverse side effects of amitriptyline, which are caused by antagonism of the Histamine H1 receptor, can be lessened by modifying the drug to not bind as well to H1. After many modifications of amitriptyline, I was able to create a successful compound that increased the affinity to 5-HT1A and 5-HT2A, as well as decreased the affinity to H1. These properties would make the medication more usable for a person with a comorbidity of POTS and migraines.
