:Dibenzepin
{{Short description|Chemical compound}}
{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 447436237
| IUPAC_name = 10-(2-(dimethylamino)ethyl)-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
| image = Dibenzepin Structural Formula V1.svg
| image_class = skin-invert-image
| alt = Skeletal formula of dibenzepin
| width = 190
| image2 = Dibenzepin 3D spacefill.png
| image_class2 = bg-transparent
| alt2 = Space-filling model of the dibenzepin molecule
| tradename = Noveril, Anslopax, Deprex, Ecatril, Neodit, Victoril
| Drugs.com = {{drugs.com|international|dibenzepin}}
| pregnancy_category =
| legal_AU =
| legal_BR = C1
| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}
| legal_CA =
| legal_DE =
| legal_NZ =
| legal_UK =
| legal_US =
| legal_EU =
| legal_UN =
| legal_status = Rx-only
| routes_of_administration = Oral
| bioavailability = 25%
| protein_bound = 80%
| metabolism = Hepatic
| elimination_half-life = 5 hours
| excretion = Urine (80%), feces (20%)
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 4498-32-2
| ATC_prefix = N06
| ATC_suffix = AA08
| PubChem = 9419
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9048
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1442422
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 510SJZ1Y6L
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07812
| C=18 | H=21 | N=3 | O=1
| SMILES = O=C2c1c(cccc1)N(c3c(N2CCN(C)C)cccc3)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H21N3O/c1-19(2)12-13-21-17-11-7-6-10-16(17)20(3)15-9-5-4-8-14(15)18(21)22/h4-11H,12-13H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QPGGEKPRGVJKQB-UHFFFAOYSA-N
}}
Dibenzepin, sold under the brand name Noveril among others, is a tricyclic antidepressant (TCA) used widely throughout Europe 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 | isbn = 3-88763-075-0 | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=dibenzepin&pg=PA323}}{{cite book | vauthors = Sittig M | title = Pharmaceutical manufacturing encyclopedia | publisher = Noyes Publications | location = Park Ridge, N.J., U.S.A | year = 1988 | isbn = 0-8155-1144-2 | url = https://books.google.com/books?id=X2EyLsG4bcUC&q=dibenzepin&pg=PA470 }}{{cite journal | vauthors = Beresewicz M, Bidzińska E, Koszewska I, Puzyński S | title = [Results of using tricyclic antidepressive drugs in the treatment of endogenous depression (comparative analysis of 7 drugs)] | language = pl | journal = Psychiatria Polska | volume = 25 | issue = 3–4 | pages = 13–8 | year = 1991 | pmid = 1687987 }} It has similar efficacy and effects relative to other TCAs like imipramine but with fewer side effects.{{cite web | url = http://www.health.gov.il/units/pharmacy/trufot/alonim/2107.pdf | title = Novartis (dibenzepin) - Prescribing Information}}{{cite book | vauthors = Paloucek FP, Leikin JB | title = Poisoning and Toxicology Handbook, Fourth Edition (Poisoning and Toxicology Handbook (Leiken & Paloucek's)) | publisher = Informa Healthcare | year = 2007 | isbn = 978-1-4200-4479-9 | url = https://books.google.com/books?id=0Bw2UJTC_uMC&q=dibenzepin&pg=PA242}}{{cite journal | vauthors = Gowardman M, Brown RA | title = Dibenzepin and amitriptyline in depressive states: comparative double-blind trial | journal = The New Zealand Medical Journal | volume = 83 | issue = 560 | pages = 194–7 |date=March 1976 | pmid = 6928 }}{{cite journal | vauthors = Baron DP, Unger HR, Williams HE, Knight RG | title = A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline | journal = The New Zealand Medical Journal | volume = 83 | issue = 562 | pages = 273–4 |date=April 1976 | pmid = 8749 }}
Medical uses
Dibenzepin is used mainly in the treatment of major depressive disorder.
Like other TCAs, dibenzepin may have potential use in the treatment of chronic neuropathic pain.
Overdose
{{Main|Tricyclic antidepressant overdose}}
As TCAs 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 TCAs, 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, TCAs are rarely selected as the first-line treatment for depression.
Pharmacology
=Pharmacodynamics=
{{See also|Pharmacology of antidepressants|Tricyclic antidepressant#Binding profiles}}
Dibenzepin acts as a selective norepinephrine reuptake inhibitor (NRI), with similar potency to that of imipramine.{{cite journal | vauthors = Barth N, Manns M, Muscholl E | title = Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart | journal = Naunyn-Schmiedeberg's Arch. Pharmacol. | volume = 288 | issue = 2–3 | pages = 215–31 | year = 1975 | pmid = 1161046 | doi = 10.1007/bf00500528| s2cid = 11641400 }} It is also a potent antihistamine. The drug has weak or negligible effects on serotonin and dopamine reuptake.{{cite journal | vauthors = Rao ML, Frahnert C, Zagorski O | title = Initial serotonin transport into viable platelets and imipramine binding to platelet membranes | journal = J Neural Transm (Vienna) | volume = 109 | issue = 5–6 | pages = 547–56 | year = 2002 | pmid = 12111448 | doi = 10.1007/s007020200045 | s2cid = 9703461 }} Unlike many other TCAs, dibenzepin has no antiadrenergic (α1, α2), antiserotonergic (5-HT1A, 5-HT2A), or antidopaminergic effects and has few or no anticholinergic ({{abbrlink|mACh|muscarinic acetylcholine receptor}}) effects.
=Pharmacokinetics=
Therapeutic levels of dibenzepin are approximately 85 to 850 nM. Its plasma protein binding is approximately 80%.{{cite book| vauthors = Aldenhoff J | chapter = Medikamente und andere Behandlungsverfahren |title=Psychiatrische Therapie | chapter-url = https://books.google.com/books?id=Ag8-W3IqG4wC&pg=PA270 |year=2007|publisher=Schattauer Verlag|isbn=978-3-7945-2189-0|pages=270–}}
History
Dibenzepin was first introduced, in Switzerland and West Germany, in 1965. It was introduced in France in 1967, in Italy in 1968, in the United Kingdom in 1970, and in Japan in 1975. It was also marketed in a number of other countries, including Portugal and Israel.
Society and culture
=Brand names=
References
{{Reflist|30em}}
External links
- {{cite web | url = http://www.health.gov.il/units/pharmacy/trufot/alonim/2107.pdf | title = Novartis - Noveral (dibenzepin) - Prescribing Information}}
{{Antidepressants}}
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{{Tricyclics}}
Category:Dimethylamino compounds
Category:H1 receptor antagonists