L'amitriptilina agisce principalmente come un [[inibitore del reuptake della serotonina-norepinefrina]], con forti effetti sul [[:en:serotonin transporter|trasportatore della serotonina]], ed effetti moderati sul [[:en:norepinephrine transporter|trasportatore della norepinefrina]].<ref>http://www.cnsforum.com/content/pictures/imagebank/hirespng/antidep_uptake_specific.png</ref><ref name="pmid9537821">{{Cite pmid|9537821}}</ref> Ha un effetto trascurabile sul [[:en:dopamine transporter|trasportatore della dopamina]] e dunque non agisce sul "[[Ricaptazione|reuptake]]" della [[dopamina]], dal momento che è circa 1.000 volte più debole sul reuptake della dopamina rispetto a quello della [[serotonina]].<ref name="pmid9537821"/>
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AmitriptylineInoltre additionallyl'amitriptilina functionsfunziona ascome aun [[:en:5-HT2A receptor|recettore 5-HT<sub>2A</sub>]], [[:en:5-HT2C receptor|5-HT<sub>2C</sub>]], [[:en:5-HT6 receptor|5-HT<sub>6</sub>]], [[:en:5-HT7 receptor|5-HT<sub>7</sub>]], [[:en:a1-adrenergic receptor|α<sub>1</sub>-adrenergic]], [[:en:H1 receptor|H<sub>1</sub>]], ande [[:en:muscarinic acetylcholine receptor|mAChrecettore receptormACh]] come [[:en:receptor antagonist|antagonistantagonista recettoriale]], ande come [[sigma-1 receptor|recettore σ<sub>1</sub> receptor]] [[agonistagonista]].<ref name="pmid9400006">{{Cite pmid|9400006}}</ref><ref name="bookEssentials of clinical psychopharmacology">{{cite book | author = Alan F. Schatzberg, Charles B. | title = Essentials of clinical psychopharmacology | publisher = American Psychiatric Pub | year = 2006 | page = 7 | isbn = 1585622435, 9781585622436 }}</ref><ref name="pmid11561066">{{Cite pmid|11561066}}</ref><ref name="pmid17689532">{{Cite pmid|17689532}}</ref> It has also been shown to be a relatively weak [[NMDA receptor]] [[NMDA receptor antagonist|negative allosteric modulator]] at the same [[binding site]] as [[phencyclidine]].<ref name="pmid2568580">{{Cite pmid|2568580}}</ref> Amitriptyline inhibits [[sodium channel]]s, [[L-type calcium channel|<small>L</small>-type calcium channel]]s, and [[Kv1.1|K<sub>v</sub>1.1]], [[Kv7.2|K<sub>v</sub>7.2]], and [[Kv7.3|K<sub>v</sub>7.3]] [[voltage-gated potassium channel]]s, and therefore acts as a [[sodium channel blocker|sodium]], [[calcium channel blocker|calcium]], and [[potassium channel blocker|potassium]] [[channel blocker]] as well.<ref name="pmid9435180">{{Cite pmid|9435180}}</ref><ref name="pmid18048694">{{Cite pmid|18048694}}</ref><ref name="pmid17456683">{{cite journal | author = Punke MA, Friederich P | title = Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels | journal = Anesthesia and Analgesia | volume = 104 | issue = 5 | pages = 1256–64, tables of contents | year = 2007 | month = May | pmid = 17456683 | doi = 10.1213/01.ane.0000260310.63117.a2 | url = http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17456683}}</ref>
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Recently, amitriptyline has been demonstrated to act as an [[agonist]] of the [[TrkA]] and [[TrkB|TrkB receptor]]s.<ref name="pmid19549602">{{Cite pmid|19549602}}</ref> It promotes the [[heterodimerization]] of these [[protein]]s in the absence of [[Nerve Growth Factor|NGF]] and has potent [[neurotrophic]] activity both ''in-vivo'' and ''in-vitro'' in mouse models.<ref name="pmid19549602"/><ref>http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20A)/AMITRIPTYLINE.html</ref>
