Amitriptyline (Elavil)

One thing about chemists is that they are molecule manipulators and they can produce an awful lot for you but as you know you've got to screen a whole lot before you get one that looks like its worth doing work beyond an animal stage. So the end result was we got a lot of tricylics, got a lot of phenothiazines, a lot of thioxanthenes and so on - Frank Ayd MD

Amitriptyline (Elavil)
Amitriptyline (Elavil)

image by: Aila Nicolle

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Classics in Chemical Neuroscience: Amitriptyline

Amitriptyline was the second tricyclic antidepressant to appear on the market for major depressive disorder under the brand name Elavil in 1961. Since its emergence, amitriptyline has been an effective therapeutic in various disease states and disorders but has also been a concerning source of cardiotoxicity. Amitriptyline inhibits serotonin and norepinephrine reuptake as well as produces off-target activity at histaminergic, muscarinic, and various other receptors. Its role as a modulator of monoamines helped further establish the monoamine theory to understand various mood disorders, paving the way for the now more common selective serotonin/norepinephrine reuptake inhibitors.

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 Classics in Chemical Neuroscience: Amitriptyline

In this review, we will discuss amitriptyline's synthesis, manufacturing information, drug metabolism, pharmacology, adverse effects, and its history and importance in therapy to present amitriptyline as a true classic in chemical neuroscience.

National Headache Foundation

Amitriptyline is included in a group of medications classified as tricyclic antidepressants. Amitriptyline is one of the first successful medications in this class to be developed. It was discovered in the late 1930s before scientists had today’s understanding of the chemistry of the brain. This drug was developed as a way to reduce anxiety. Frequently, people with depression are often very anxious. When amitriptyline was given to patients with anxiety, it also improved the depression. This result prompted further research and the development of newer agents to treat depression.


If QRS exceeds 100 msec, intravenous sodium bicarbonate is the appropriate intervention. Sodium bicarbonate is cardioprotective (it increases extracellular sodium concentration) and diminishes the effect of amitriptyline on the cardiac membrane, resulting in less sodium channel blockage. Alkalization favors the neutral form of amitriptyline and decreases the amount of active cyclic antidepressants.

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