Classics in Chemical Neuroscience: Amitriptyline

Abstract

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. 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.

Inhibition of Microglial Activation by Amitriptyline and Doxepin in Interferon-β Pre-Treated Astrocyte–Microglia Co-Culture Model of Inflammation

“…Even if doxepin and amitriptyline are not considered as a first choice for the treatment of depression, they offer further valuable effects concerning symptoms of insomnia, neuropathic pain, chronic headache and spastic pain in combination with sleep and anxiety disorders, which can occur in patients with MS together with additional symptoms of depression [ 28 , 29 , 30 , 31 , 72 ]. The advantage of the old antidepressants is that they are not selective, as with the modern serotonin re-uptake inhibitors, but have more effects.…”

“…Both are tricyclic antidepressants. Amitriptyline inhibits serotonin and norepinephrine re-uptake, but also further effects, e.g., on histaminergic and muscarinic receptors, are known [ 28 ]. Additionally, amitriptyline is used for the treatment of neuropathic pain, migraine and tension headache [ 29 ].…”

Investigation of the performance of cross-linked poly(acrylic acid) and poly(methacrylic acid) as efficient adsorbents in SPE columns for simultaneous preconcentration of tricyclic antidepressants in water samples

“…It is also noteworthy that NOR is a product of AMT degradation, which Analytical Methods Paper can be considered one of the most consumed tricyclic antidepressants in the world. [42][43][44][45] The recoveries obtained from spiked samples with the TCAs at concentrations of 0.75 and 6.00 mg L −1 are also summarized in Table 5. The recovery percentages ranged from 86.7 to 116.0% when using poly(AA-co-EGDMA) and from 88.0 to 113.3% for poly(MAA-co-EGDMA), attesting the accuracy of the proposed method for the interference-free determination of TCAs in water from different sources.…”

Growing Utilization of Radical Chemistry in the Synthesis of Pharmaceuticals

“…Metabolizing inside the body to nortriptyline, a stronger norepinephrine reuptake inhibitor, it restricts the serotonin transporter (SERT) and norepinephrine transporter (NET), thereby interfering with neuronal reuptake of serotonin and norepinephrine. The prolong presence of these neurotransmitters over the serotonergic and adrenergic neurons exhibits the antidepressant activity of amitriptyline ( 37.4 ) [142] . Avoiding the use of Grignard reagents and for direct installation of the ethylamine group onto the alkene functionality of the tricyclic structural motif, König and Xiao with co‐workers in 2019, demonstrated a dual Ni‐ and photocatalyzed coupling reaction of unactivated alkyl bromides with vinyl bromides under light illuminated mild conditions to afford the corresponding alkene products.…”