Dibenzepin

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Dibenzepin
Dibenzepin.png
Systematic (IUPAC) name
10-(2-(dimethylamino)ethyl)-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
Clinical data
AHFS/Drugs.com International Drug Names
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 25% (Oral)
Protein binding 80%
Metabolism Hepatic
Half-life 5 hours
Excretion Urine (80%), Feces (20%)
Identifiers
CAS number 4498-32-2 YesY
ATC code N06AA08
PubChem CID 9419
ChemSpider 9048 YesY
UNII 510SJZ1Y6L YesY
KEGG D07812 YesY
Chemical data
Formula C18H21N3O 
Mol. mass 295.379 g/mol
 YesY (what is this?)  (verify)

Dibenzepin (Noveril, Anslopax, Deprex, Ecatril, Neodit, Victoril) is a tricyclic antidepressant (TCA) used widely throughout Europe for the treatment of depression.[1][2][3] It has similar efficacy and effects relative to other TCAs like imipramine but with fewer side effects.[4][5][6][7] Dibenzepin acts as a norepinephrine reuptake inhibitor, potent antihistamine, and weak anticholinergic.[4][5][8] It lacks any 5-HT2 antagonistic properties.[9]

Chronic Pain[edit]

Like other tricyclic antidepressants, dibenzepin may have potential use in the treatment of chronic neuropathic pain.

Overdose[edit]

As tricyclic antidepressants have a relatively narrow therapeutic index, the likelihood of overdose (both accidental and intentional) is fairly high and should be considered carefully by the prescribing physician prior to patient use. Symptoms of overdose are similar to those of other tricyclic antidepressants, with cardiac toxicity (due to inhibition of sodium and calcium channels) generally occurring before the threshold for serotonin syndrome is reached. Due to this risk, tricyclic antidepressants are rarely selected as the first line treatment for depression.

Synthesis[edit]

The Ullmann reaction provides the key for preparing the diaryl-amine or -ether starting materials in this series.

Dibenzepin synthesis.png

Copper catalyzed coupling of methyl N-methylanthranilate () with nitrobromobenzene () leads to the arylaniline (). The ester is then saponified () and the nitro group reduced to the corresponding amine (). That product cyclizes to the lactam () on heating. A strong base preferentially removes the proton on the lactam nitrogen to form an anion. Alkylation with 2-chloroethyldimethylamine then affords dibenzepin (), a compound that shows antidepressant activity.[10]

See also[edit]

References[edit]

  1. ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0. 
  2. ^ Sittig, Marshall (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. ISBN 0-8155-1144-2. 
  3. ^ Beresewicz M, Bidzińska E, Koszewska I, Puzyński S (1991). "[Results of using tricyclic antidepressive drugs in the treatment of endogenous depression (comparative analysis of 7 drugs)]". Psychiatria Polska (in Polish) 25 (3-4): 13–8. PMID 1687987. 
  4. ^ a b "Novartis (dibenzepin) - Prescribing Information". 
  5. ^ a b Paloucek, Frank P.; Leikin, Jerrold B. (2007). Poisoning and Toxicology Handbook, Fourth Edition (Poisoning and Toxicology Handbook (Leiken & Paloucek's)). Informa Healthcare. ISBN 1-4200-4479-6. 
  6. ^ Gowardman M, Brown RA (March 1976). "Dibenzepin and amitriptyline in depressive states: comparative double-blind trial". The New Zealand Medical Journal 83 (560): 194–7. PMID 6928. 
  7. ^ Baron DP, Unger HR, Williams HE, Knight RG (April 1976). "A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline". The New Zealand Medical Journal 83 (562): 273–4. PMID 8749. 
  8. ^ Rehavi M, Maayani S, Goldstein L, Assael M, Sokolovsky M (August 1977). "Antimuscarinic properties of antidepressants: dibenzepin (Noveril)". Psychopharmacology 54 (1): 35–8. doi:10.1007/BF00426538. PMID 20647. 
  9. ^ Closse A, Jaton AL (July 1984). "Investigation of the influence of lithium upon the down-regulation of serotonin2 receptors in rat frontal cortex induced by long-term treatment with dibenzepin, an antidepressant without appreciable affinity to serotonin2 receptors". Naunyn-Schmiedeberg's Archives of Pharmacology 326 (4): 291–3. doi:10.1007/bf00501432. PMID 6148707. 
  10. ^ Hunziker, F.; Lauener, H.; Schmutz, J.; Arzneim. Forsch. 1963, 13, 324.

External links[edit]