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Dibenzepin
Chemical compound
Chemical compound
| Field | Value | |||
|---|---|---|---|---|
| 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 | ||||
| legal_AU | ||||
| legal_BR | C1 | |||
| legal_BR_comment | ||||
| legal_CA | ||||
| legal_DE | ||||
| legal_NZ | ||||
| legal_UK | ||||
| legal_US | ||||
| 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 | ||||
| CAS_number | 4498-32-2 | |||
| ATC_prefix | N06 | |||
| ATC_suffix | AA08 | |||
| PubChem | 9419 | |||
| ChemSpiderID_Ref | ||||
| ChemSpiderID | 9048 | |||
| ChEMBL_Ref | ||||
| ChEMBL | 1442422 | |||
| UNII_Ref | ||||
| UNII | 510SJZ1Y6L | |||
| KEGG_Ref | ||||
| KEGG | D07812 | |||
| C | 18 | H=21 | N=3 | O=1 |
| SMILES | O=C2c1c(cccc1)N(c3c(N2CCN(C)C)cccc3)C | |||
| StdInChI_Ref | ||||
| 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 | ||||
| StdInChIKey | QPGGEKPRGVJKQB-UHFFFAOYSA-N |
| Drugs.com =
| elimination_half-life = 5 hours
Dibenzepin, sold under the brand name Noveril among others, is a tricyclic antidepressant (TCA) used widely throughout Europe for the treatment of depression. It has similar efficacy and effects relative to other TCAs like imipramine but with fewer side effects.
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 article: 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
| Site | Ki (nM) | Species | Ref | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ND | ND | ND | ||||||||||
| **** | ND | ND | ||||||||||
| 100,000 | Rat | vauthors = Hyttel J | title = Inhibition of [3H]dopamine accumulation in rat striatal synaptosomes by psychotropic drugs | journal = Biochem. Pharmacol. | volume = 27 | issue = 7 | pages = 1063–8 | year = 1978 | pmid = 656154 | doi = 10.1016/0006-2952(78)90159-4}} | ||
| 5-HT1A | 10,000 | Rat | vauthors = Closse A, Jaton AL | title = 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 | journal = Naunyn-Schmiedeberg's Arch. Pharmacol. | volume = 326 | issue = 4 | pages = 291–3 | year = 1984 | pmid = 6148707 | doi = 10.1007/bf00501432 | s2cid = 24925602 }} |
| 5-HT2A | ≥1,500 | Rat | ||||||||||
| 5-HT2C | ND | ND | ND | |||||||||
| α1 | 10,000 | Rat | ||||||||||
| α2 | 10,000 | Rat | ||||||||||
| DA | 10,000 | Bovine | ||||||||||
| H1 | 23 | Human | vauthors = Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R | title = Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics | journal = Naunyn-Schmiedeberg's Arch. Pharmacol. | volume = 385 | issue = 2 | pages = 145–70 | year = 2012 | pmid = 22033803 | doi = 10.1007/s00210-011-0704-0 | s2cid = 14274150 }} |
| H2 | 1,950 | Human | ||||||||||
| H3 | 100,000 | Human | ||||||||||
| H4 | 100,000 | Human | ||||||||||
| 1,750 | Rat | vauthors = Rehavi M, Maayani S, Goldstein L, Assael M, Sokolovsky M | title = Antimuscarinic properties of antidepressants: dibenzepin (Noveril) | journal = Psychopharmacology | volume = 54 | issue = 1 | pages = 35–8 | year = 1977 | pmid = 20647 | doi = 10.1007/bf00426538 | s2cid = 27031652 }} | |
| Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
Dibenzepin acts as a selective norepinephrine reuptake inhibitor (NRI), with similar potency to that of imipramine. It is also a potent antihistamine. The drug has weak or negligible effects on serotonin and dopamine reuptake. Unlike many other TCAs, dibenzepin has no antiadrenergic (α1, α2), antiserotonergic (5-HT1A, 5-HT2A), or antidopaminergic effects and has few or no anticholinergic () effects.
Pharmacokinetics
Therapeutic levels of dibenzepin are approximately 85 to 850 nM. Its plasma protein binding is approximately 80%.
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
Dibenzepin is or was marketed mainly under the brand name Noveril. It has also been marketed under a number of other brand names, including Ansiopax, Deprex, Ecatril, Neodit, and Victoril.
References
References
- Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
- Swiss Pharmaceutical Society. (2000). "Index Nominum 2000: International Drug Directory (Book with CD-ROM)". Medpharm Scientific Publishers.
- (1988). "Pharmaceutical manufacturing encyclopedia". Noyes Publications.
- (1991). "[Results of using tricyclic antidepressive drugs in the treatment of endogenous depression (comparative analysis of 7 drugs)]". Psychiatria Polska.
- "Novartis (dibenzepin) - Prescribing Information".
- (2007). "Poisoning and Toxicology Handbook, Fourth Edition (Poisoning and Toxicology Handbook (Leiken & Paloucek's))". Informa Healthcare.
- (March 1976). "Dibenzepin and amitriptyline in depressive states: comparative double-blind trial". The New Zealand Medical Journal.
- (April 1976). "A double blind study of the antidepressants dibenzepin (Noveril) and amitriptyline". The New Zealand Medical Journal.
- "PDSP Ki Database". University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.
- (1978). "Inhibition of [3H]dopamine accumulation in rat striatal synaptosomes by psychotropic drugs". Biochem. Pharmacol..
- (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 Arch. Pharmacol..
- (2012). "Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Arch. Pharmacol..
- (1977). "Antimuscarinic properties of antidepressants: dibenzepin (Noveril)". Psychopharmacology.
- (1975). "Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart". Naunyn-Schmiedeberg's Arch. Pharmacol..
- (2002). "Initial serotonin transport into viable platelets and imipramine binding to platelet membranes". J Neural Transm (Vienna).
- (2007). "Psychiatrische Therapie". Schattauer Verlag.
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