Noxiptiline Explained

Noxiptiline (brand names Agedal, Elronon, Nogedal), also known as noxiptyline and dibenzoxine, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1970s for the treatment of depression.^{[1] [2] [3]} It has imipramine-like effects,^[4] acting as a serotonin and norepinephrine reuptake inhibitor, among other properties.^{[5] [6]} Of the TCAs, noxiptiline has been described as one of the most effective, rivaling amitriptyline in clinical efficacy.^{[7] [8]}

Synthesis

The ketone dibenzosuberenone (1) is treated with hydroxylamine (2) to give its ketoxime (3). Base-catalyzed alkylation with (4) yields noxiptiline.^{[9] [10] [11]}

Notes and References

1. Book: Swiss Pharmaceutical Society . Index Nominum 2000: International Drug Directory (Book with CD-ROM) . Medpharm Scientific Publishers . Boca Raton . 2000 . 753 . 3-88763-075-0 .
2. Book: Aronson JK . Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects) . Elsevier Science . Amsterdam . 2008 . 34 . 978-0-444-53266-4 .
3. Book: Dictionary of organic compounds . Chapman & Hall . London . 1996 . 4868 . 0-412-54090-8 .
4. Book: Mutschler E . Antidepressants . Drug actions: basic principles and therapeutic aspects . Medpharm Scientific Pub . Stuttgart, Germany . 1995 . 127 . 0-8493-7774-9 . https://books.google.com/books?id=IvN4mZxraMkC&q=noxiptiline&pg=PA127 . January 30, 2013.
5. Book: Olivier B, Soudijn W, van Wijngaarden I . Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors . Progress in Drug Research . Jucker E, Ren S, Soudijn W, van Wijngaarden I, Kumari M, Poyner D, Bushfield M, Horikoshi H, Fujiwara T . 54 . 59–119 . 2000 . 10857386 . 10.1007/978-3-0348-8391-7_3 . https://books.google.com/books?id=gwhdUGoO6KwC&q=noxiptiline%20fluvoxamine&pg=PA81 . Birkhauser . Boston . 3-7643-6113-1 .
6. Barth N, Manns M, Muscholl E . Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart . Naunyn-Schmiedeberg's Archives of Pharmacology . 288 . 2–3 . 215–231 . 1975 . 1161046 . 10.1007/BF00500528 . 11641400 .
7. Beresewicz M, Bidzińska E, Koszewska I, Puzyński S . [Results of using tricyclic antidepressive drugs in the treatment of endogenous depression (comparative analysis of 7 drugs)] . pl . Psychiatria Polska . 25 . 3–4 . 13–18 . 1991 . 1687987 .
8. Lingjaerde O, Asker T, Bugge A, Engstrand E, Eide A, Grinaker H, Herlofsen H, Ose E, Ofsti E . 6 . Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline . Pharmakopsychiatrie, Neuro-Psychopharmakologie . 8 . 1 . 26–35 . January 1975 . 788000 . 10.1055/s-0028-1094440 . 44886111 .
9. Aichinger G, Behner O, Hoffmeister F, Schütz S . Basic tricyclic oxyiminoethers and their pharmacological properties . Arzneimittel-Forschung . 19 . Suppl 5a:838+ . June 1969 . 5819763 . DE .
10. Basic oximes and their preparation . Schütz S, Behner O, Hoffmeister F . US . 3963778 . 1976-06-15 . Bayer AG .
11. Wylie BB, Isaacson EI, Delgado JN . Synthesis of oxime esters and ethers as potential psychotropic agents . Journal of Pharmaceutical Sciences . 54 . 9 . 1373–1376 . September 1965 . 5881239 . 10.1002/jps.2600540932 .