Amitriptylinoxide

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.[1]

Amitriptylinoxide

Clinical data
Trade names	Amioxid, Ambivalon, Equilibrin
Routes of administration	Oral
ATC code	none
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 3-(10,11-dihydro- 5H-dibenzo[a,d]cycloheptene- 5-ylidene)- N,N-dimethyl- 1-propanamine N-oxide
CAS Number	4317-14-0
PubChem CID	20313
ChemSpider	19137
UNII	TYR2U59WMA
KEGG	D07449
ChEMBL	ChEMBL627
CompTox Dashboard (EPA)	DTXSID50195758
ECHA InfoCard	100.119.550
Chemical and physical data
Formula	C20H23NO
Molar mass	293.410 g·mol^−1
3D model (JSmol)	Interactive image
SMILES [O-][N+](C)(C)CC/C=C2/c1c(cccc1)CCc3c2cccc3
InChI InChI=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 Key:ZPMKQFOGINQDAM-UHFFFAOYSA-N
(verify)

Amitriptylinoxide is both an analogue and metabolite of amitriptyline, and has similar effects as well as equivalent efficacy as an antidepressant.[2][3][4][5] 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.[2][3][4][5][6][7]

In receptor binding assays, amitripylinoxide 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.[8][9][10]

Amitriptylinoxide has been said to be a prodrug of amitriptyline.[11]

See also

• Imipraminoxide

References

1. Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. p. 49. ISBN 3-88763-075-0.
2. Rapp W (September 1978). "Comparative trial of amitriptyline-N-oxide and amitriptyline in the treatment of out-patients with depressive syndromes". Acta Psychiatrica Scandinavica. 58 (3): 245–55. doi:10.1111/j.1600-0447.1978.tb06936.x. PMID 360779. S2CID 12666498.
3. Tegeler J, Klieser E, Lehmann E, Heinrich K (January 1990). "Double-blind study of the therapeutic efficacy and tolerability of amitriptylinoxide in comparison with amitriptyline". Pharmacopsychiatry. 23 (1): 45–9. doi:10.1055/s-2007-1014481. PMID 2179974.
4. Godt HH, Fredslund-Andersen K, Edlund AH (1971). "[Amitriptyline N-oxide. A new antidepressant. A clinical double-blind trial in comparison with amitriptyline]". Nordisk Psykiatrisk Tidsskrift. Nordic Journal of Psychiatry (in Danish). 25 (3): 237–46. doi:10.3109/08039487109094663. PMID 4945956.
5. Aronson, Jeffrey Kenneth (2008). Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects). Amsterdam: Elsevier Science. p. 30. ISBN 978-0-444-53266-4.
6. Wenzl H, Graf E, Sieck A (1978). "Central nervous effects of a new tricyclic antidepressant (amitriptylinoxide)". Arzneimittel-Forschung. 28 (10b): 1874–9. PMID 261811.
7. Dencker SJ (1971). "[Clinical trial with imipramine-N-oxide and amitriptyline-N-oxide]". Nordisk Psykiatrisk Tidsskrift. Nordic Journal of Psychiatry (in Swedish). 25 (5): 463–70. doi:10.3109/08039487109094696. PMID 4947298.
8. Borbe HO, Zierenberg O (September 1985). "Amitriptylinoxide: receptor-binding profile compared with other antidepressant drugs". Pharmacopsychiatry. 18 (5): 314–9. doi:10.1055/s-2007-1017388. PMID 2996040.
9. Maj J, Vetulani J, Michaluk J, Rogóz Z, Skuza G (November 1982). "Central action of amitriptyline N-oxide". Pharmacopsychiatria. 15 (6): 187–91. doi:10.1055/s-2007-1019536. PMID 6185962.
10. Hyttel J, Christensen AV, Fjalland B (July 1980). "Neuropharmacological properties of amitriptyline, nortriptyline and their metabolites". Acta Pharmacologica et Toxicologica. 47 (1): 53–7. doi:10.1111/j.1600-0773.1980.tb02025.x. PMID 7395525.
11. Pavel Anzenbacher; Ulrich M. Zanger (23 February 2012). Metabolism of Drugs and Other Xenobiotics. John Wiley & Sons. pp. 302–. ISBN 978-3-527-64632-6.