美國(guó)埃默里大學(xué)科研人員最近研究發(fā)現(xiàn),，被廣泛用作抗抑郁藥物和止痛劑的阿米替林可直接刺激腦部神經(jīng)細(xì)胞生長(zhǎng),，從而促進(jìn)大腦發(fā)育。
實(shí)驗(yàn)表明，阿米替林能直接促進(jìn)大腦中“神經(jīng)生長(zhǎng)因子”的發(fā)展,，維持神經(jīng)細(xì)胞中的含氧量和葡萄糖含量，從而激發(fā)神經(jīng)細(xì)胞向外伸展神經(jīng)突,，以連結(jié)其他神經(jīng)細(xì)胞,。另外，阿米替林還能抑制神經(jīng)毒素紅藻氨酸的產(chǎn)生,。這顯示了它不同于很多抗抑郁藥物的藥效機(jī)制,。
阿米替林是一種三環(huán)類(lèi)抗抑郁劑，目前被廣泛用于治療偏頭痛和由糖尿病引發(fā)的神經(jīng)性疾病,。
這項(xiàng)研究結(jié)果將發(fā)表在最新一期美國(guó)《化學(xué)與生物學(xué)》雜志上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Chemistry & Biology, Volume 16, Issue 6, 644-656, 26 June 2009 doi:10.1016/j.chembiol.2009.05.010
Amitriptyline is a TrkA and TrkB Receptor Agonist that Promotes TrkA/TrkB Heterodimerization and Has Potent Neurotrophic Activity
Sung-Wuk Jang1,Xia Liu1,Chi-Bun Chan1,David Weinshenker2,Randy A. Hall3,Ge Xiao4andKeqiang Ye1,,
1 Department of Pathology and Laboratory Medicine, Emory University, 615 Michael Street, Atlanta, GA 30322, USA
2 Department of Human Genetics, Emory University, 615 Michael Street, Atlanta, GA 30322, USA
3 Department of Pharmacology, Emory University, 615 Michael Street, Atlanta, GA 30322, USA
4 Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA 30341, USA
Neurotrophins, the cognate ligands for the Trk receptors, are homodimers and induce Trk dimerization through a symmetric bivalent mechanism. We report here that amitriptyline, an antidepressant drug, directly binds TrkA and TrkB and triggers their dimerization and activation. Amitriptyline, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes TrkA autophosphorylation inprimary neurons and induces neurite outgrowth in PC12 cells. Amitriptyline binds the extracellular domain of both TrkA and TrkB and promotes TrkA-TrkB receptor heterodimerization. Truncation of amitriptyline binding motif on TrkA abrogates the receptor dimerization by amitriptyline. Administration of amitriptyline to mice activates both receptors and significantly reduces kainic acid-triggered neuronal cell death. Inhibition of TrkA, but not TrkB, abolishes amitriptyline's neuroprotective effect without impairing its antidepressant activity. Thus, amitriptyline acts as a TrkA and TrkB agonist and possesses marked neurotrophic activity.
