Amitriptyline Directly Stimulates Brain Growth Factor Receptors

Amitriptyline (or Amitryptyline) hydrochloride (also known as Elavil, Tryptanol, Endep, Elatrol, Tryptizol, Trepiline, Laroxyl, Saroten, Triptyl, Redomex) is a tricyclic antidepressant.

Amitriptyline is used in the US and UK to prevent migraines. It is also used as sleeping aid and for treatment of major depression.

It works by by increasing the levels of serotonin and norepinephrine in the brain. But the delay required for antidepressants to work has led scientists to the idea that a secondary effect, pushing neurons to survive and grow, must occur indirectly.

The finding that amitriptyline can directly stimulate molecules that help neurons grow and resist toxins suggests a separate mechanism by which some antidepressant and pain relief compounds may function.

It appears that Amitriptyline can imitate NGF (nerve growth factor) protein in the brain. The research was performed by Keqiang Ye, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine, and colleagues.

In laboratory tests, amitriptyline could protect neurons from oxygen and glucose deprivation or the toxin kainic acid. Only amitriptyline, and not other antidepressants, could duplicate NGF's ability to stimulate neurons to send out "neurites," small projections thought to be the beginnings of connections to other neurons.

Amitriptyline directly binds TrkA and a related molecule called TrkB, researches found. Amitriptyline could also bring together a mismatched pair of TrkA and TrkB.

How the findings translate to practical use is still unclear. NGF cannot cross the blood-brain barrier so finding a substitute with similar properties is highly desirable. On the other hand, since amitriptyline binds to TrkB as well as to TrkA while NGF bind two TrkA molecules, using amitriptyline as a substitute might result in unforeseen side effects.

The research shows promise but farther studies are required.

Reference: S-W Jang, X. Liu, C-B Chan, D. Weinshenker, R.A. Hall, G. Xiao and K. Ye. Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterdodimerization and has potent neurotrophic activity.
Chemistry and Biology, 16, x-y (2009).

link: Antidepressant Directly Stimulates Brain Growth Factor Receptors