:Amitriptylinoxide

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 437200894

| IUPAC_name = 3-(10,11-dihydro- 5H-dibenzo[a,d]cycloheptene- 5-ylidene)- N,N-dimethyl- 1-propanamine N-oxide

| image = Amitriptylinoxide.png

| image_class = skin-invert-image

| alt = Skeletal formula of amitriptylinoxide

| width = 200

| image2 = Amitriptylinoxide-3D-balls.png

| alt2 = Ball-and-stick model of the amitriptylinoxide molecule

| tradename = Amioxid, Ambivalon, Equilibrin

| legal_status = Rx-only

| routes_of_administration = Oral

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 4317-14-0

| ATC_prefix = N06

| ATC_suffix = AA25

| PubChem = 20313

| ChEBI = 135224

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 19137

| DrugBank = DB13114

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = TYR2U59WMA

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D07449

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 627

| C=20 | H=23 |N=1 | O=1

| SMILES = [O-][N+](C)(C)CC/C=C2/c1c(cccc1)CCc3c2cccc3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C20H23NO/c1-21(2,22)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = ZPMKQFOGINQDAM-UHFFFAOYSA-N

}}

Amitriptylinoxide (brand names Amioxid, Ambivalon, Equilibrin), or amitriptyline N-oxide, is a tricyclic antidepressant (TCA) which was introduced in Europe in the 1970s for the treatment of depression.{{cite book | author = Swiss Pharmaceutical Society | title = Index Nominum 2000: International Drug Directory (Book with CD-ROM) | publisher = Medpharm Scientific Publishers | location = Boca Raton | year = 2000 | page = 49 | isbn = 3-88763-075-0 | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=amitriptylinoxide&pg=PA49}}

Amitriptylinoxide is both an analogue and metabolite of amitriptyline, and has similar effects as well as equivalent efficacy as an antidepressant.{{cite journal | author = Rapp W | title = Comparative trial of amitriptyline-N-oxide and amitriptyline in the treatment of out-patients with depressive syndromes | journal = Acta Psychiatrica Scandinavica | volume = 58 | issue = 3 | pages = 245–55 |date=September 1978 | pmid = 360779 | doi = 10.1111/j.1600-0447.1978.tb06936.x| s2cid = 12666498 }}{{cite journal | vauthors = Tegeler J, Klieser E, Lehmann E, Heinrich K | title = Double-blind study of the therapeutic efficacy and tolerability of amitriptylinoxide in comparison with amitriptyline | journal = Pharmacopsychiatry | volume = 23 | issue = 1 | pages = 45–9 |date=January 1990 | pmid = 2179974| doi = 10.1055/s-2007-1014481| s2cid = 956047 }}{{cite journal | vauthors = Godt HH, Fredslund-Andersen K, Edlund AH | title = [Amitriptyline N-oxide. A new antidepressant. A clinical double-blind trial in comparison with amitriptyline] | language = da | journal = Nordisk Psykiatrisk Tidsskrift. Nordic Journal of Psychiatry | volume = 25 | issue = 3 | pages = 237–46 | year = 1971 | pmid = 4945956 | doi = 10.3109/08039487109094663}}{{cite book | author = Aronson, Jeffrey Kenneth | title = Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects) | publisher = Elsevier Science | location = Amsterdam | year = 2008 | page = 30 | isbn = 978-0-444-53266-4 | url = https://books.google.com/books?id=s0XYvuPVgaAC&q=amitriptylinoxide&pg=PA30}} However, it has a faster onset of action and fewer adverse effects, including reduced drowsiness, sedation, anticholinergic symptoms like dry mouth, sweating, and dizziness, orthostatic hypotension, and cardiotoxicity.{{cite journal | vauthors = Wenzl H, Graf E, Sieck A | title = Central nervous effects of a new tricyclic antidepressant (amitriptylinoxide) | journal = Arzneimittel-Forschung | volume = 28 | issue = 10b | pages = 1874–9 | year = 1978 | pmid = 261811}}{{cite journal | author = Dencker SJ | title = [Clinical trial with imipramine-N-oxide and amitriptyline-N-oxide] | language = sv | journal = Nordisk Psykiatrisk Tidsskrift. Nordic Journal of Psychiatry | volume = 25 | issue = 5 | pages = 463–70 | year = 1971 | pmid = 4947298 | doi = 10.3109/08039487109094696}}

In receptor binding assays, amitriptylinoxide was found to have generally equivalent pharmacology to amitriptyline, acting as a serotonin and norepinephrine reuptake inhibitor, serotonin receptor antagonist, and H₁ receptor antagonist, among other properties, but with approximately 60-fold lower affinity for the α₁-adrenergic receptor, and the weakest affinity of any of the TCAs analyzed for the muscarinic acetylcholine receptors.{{cite journal | vauthors = Borbe HO, Zierenberg O | title = Amitriptylinoxide: receptor-binding profile compared with other antidepressant drugs | journal = Pharmacopsychiatry | volume = 18 | issue = 5 | pages = 314–9 |date=September 1985 | pmid = 2996040| doi = 10.1055/s-2007-1017388| s2cid = 31927039 }}{{cite journal | vauthors = Maj J, Vetulani J, Michaluk J, Rogóz Z, Skuza G | author2-link = Jerzy Vetulani | title = Central action of amitriptyline N-oxide | journal = Pharmacopsychiatria | volume = 15 | issue = 6 | pages = 187–91 |date=November 1982 | pmid = 6185962 | doi = 10.1055/s-2007-1019536| s2cid = 25823571 }}{{cite journal | vauthors = Hyttel J, Christensen AV, Fjalland B | title = Neuropharmacological properties of amitriptyline, nortriptyline and their metabolites | journal = Acta Pharmacologica et Toxicologica | volume = 47 | issue = 1 | pages = 53–7 |date=July 1980 | pmid = 7395525 | doi = 10.1111/j.1600-0773.1980.tb02025.x}}

Amitriptylinoxide has been said to be a prodrug of amitriptyline.{{cite book|author1=Pavel Anzenbacher|author2=Ulrich M. Zanger|title=Metabolism of Drugs and Other Xenobiotics|url=https://books.google.com/books?id=f-XHh17NfwgC&pg=PA302|date=23 February 2012|publisher=John Wiley & Sons|isbn=978-3-527-64632-6|pages=302–}}