Dibenzepin

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Dibenzepin
Dibenzepin Structural Formula V1.svg
Dibenzepin 3D spacefill.png
Clinical data
Trade names Noveril, Anslopax, Deprex, Ecatril, Neodit, Victoril
AHFS/Drugs.com International Drug Names
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances) [1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 25%
Protein binding 80%
Metabolism Hepatic
Elimination half-life 5 hours
Excretion Urine (80%), feces (20%)
Identifiers
  • 10-(2-(dimethylamino)ethyl)-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C18H21N3O
Molar mass 295.386 g·mol−1
3D model (JSmol)
  • O=C2c1c(cccc1)N(c3c(N2CCN(C)C)cccc3)C
  • InChI=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 Yes check.svgY
  • Key:QPGGEKPRGVJKQB-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Dibenzepin, sold under the brand name Noveril among others, is a tricyclic antidepressant (TCA) used widely throughout Europe for the treatment of depression. [2] [3] [4] It has similar efficacy and effects relative to other TCAs like imipramine but with fewer side effects. [5] [6] [7] [8]

Contents

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

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

Dibenzepin [9]
SiteKi (nM)SpeciesRef
SERT Tooltip Serotonin transporterNDNDND
NET Tooltip Norepinephrine transporterNDND [10]
DAT Tooltip Dopamine transporter>100,000Rat [11]
5-HT1A >10,000Rat [12]
5-HT2A ≥1,500Rat [12]
5-HT2C NDNDND
α1 >10,000Rat [12]
α2 >10,000Rat [12]
DA >10,000Bovine [12]
H1 23Human [13]
H2 1,950Human [13]
H3 >100,000Human [13]
H4 >100,000Human [13]
mACh Tooltip Muscarinic acetylcholine receptor1,750Rat [12] [14]
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. [10] It is also a potent antihistamine. [12] [13] The drug has weak or negligible effects on serotonin and dopamine reuptake. [15] [11] Unlike many other TCAs, dibenzepin has no antiadrenergic (α1, α2), antiserotonergic (5-HT1A, 5-HT2A), or antidopaminergic effects and has few or no anticholinergic (mACh Tooltip muscarinic acetylcholine receptor) effects. [12] [14]

Pharmacokinetics

Therapeutic levels of dibenzepin are approximately 85 to 850 nM. [13] Its plasma protein binding is approximately 80%. [16]

History

Dibenzepin was first introduced, in Switzerland and West Germany, in 1965. [3] It was introduced in France in 1967, in Italy in 1968, in the United Kingdom in 1970, and in Japan in 1975. [3] It was also marketed in a number of other countries, including Portugal and Israel. [3]

Society and culture

Brand names

Dibenzepin is or was marketed mainly under the brand name Noveril. [3] It has also been marketed under a number of other brand names, including Ansiopax, Deprex, Ecatril, Neodit, and Victoril. [3]

Related Research Articles

<span class="mw-page-title-main">Tricyclic antidepressant</span> Class of medications

Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains three rings of atoms. Tetracyclic antidepressants (TeCAs), which contain four rings of atoms, are a closely related group of antidepressant compounds.

<span class="mw-page-title-main">Maprotiline</span> Antidepressant

Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary amine. In terms of its chemistry and pharmacology, maprotiline is closely related to such-other secondary-amine TCAs as nortriptyline and protriptyline and has similar effects to them, albeit with more distinct anxiolytic effects. Additionally, whereas protriptyline tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating, mild degrees of sedation may be experienced with maprotiline.

<span class="mw-page-title-main">Amitriptyline</span> Tricyclic antidepressant

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, a variety of pain syndromes such as neuropathic pain, fibromyalgia, migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Amoxapine</span> Tricyclic antidepressant medication

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.

<span class="mw-page-title-main">Imipramine</span> Antidepressant

Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth.

<span class="mw-page-title-main">Desipramine</span> Antidepressant

Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose.

<span class="mw-page-title-main">Clomipramine</span> Antidepressant

Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most-notably obsessive–compulsive disorder but also many other disorders, including panic disorder, major depressive disorder, trichotilomania, body dysmorphic disorder and chronic pain. It has also been notably used to treat premature ejaculation and the cataplexy associated with narcolepsy.

<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18–24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Trimipramine</span> Antidepressant

Trimipramine, sold under the brand name Surmontil among others, is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or "second-generation" TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs, however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.

<span class="mw-page-title-main">Dosulepin</span> Antidepressant

Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects.

<span class="mw-page-title-main">Butriptyline</span> Atypical tricyclic antidepressant medication

Butriptyline, sold under the brand name Evadyne among others, is a tricyclic antidepressant (TCA) that has been used in the United Kingdom and several other European countries for the treatment of depression but appears to no longer be marketed. Along with trimipramine, iprindole, and amoxapine, it has been described as an "atypical" or "second-generation" TCA due to its relatively late introduction and atypical pharmacology. It was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.

<span class="mw-page-title-main">Lofepramine</span> Chemical compound

Lofepramine, sold under the brand names Gamanil, Lomont, and Tymelyt among others, is a tricyclic antidepressant (TCA) which is used to treat depression. The TCAs are so named as they share the common property of having three rings in their chemical structure. Like most TCAs lofepramine is believed to work in relieving depression by increasing concentrations of the neurotransmitters norepinephrine and serotonin in the synapse, by inhibiting their reuptake. It is usually considered a third-generation TCA, as unlike the first- and second-generation TCAs it is relatively safe in overdose and has milder and less frequent side effects.

<span class="mw-page-title-main">Protriptyline</span> Chemical compound

Protriptyline, sold under the brand name Vivactil among others, is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and attention-deficit hyperactivity disorder (ADHD). Uniquely among most of the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.

<span class="mw-page-title-main">Opipramol</span> Drug used to treat depressive and anxiety disorders

Opipramol, sold under the brand name Insidon among others, is an anxiolytic and tricyclic antidepressant that is used throughout Europe. Despite chemically being a tricyclic dibenzazepine (iminostilbene) derivative similar to imipramine, opipramol is not a monoamine reuptake inhibitor like most other tricyclic antidepressants, and instead, uniquely among antidepressants, acts primarily as a SIGMAR1 agonist. It was developed by Schindler and Blattner in 1961.

<span class="mw-page-title-main">Serotonin antagonist and reuptake inhibitor</span> Class of drug

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

<span class="mw-page-title-main">Noxiptiline</span> Chemical compound

Noxiptiline, also known as noxiptyline and dibenzoxine, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1970s for the treatment of depression. It has imipramine-like effects, acting as a serotonin and norepinephrine reuptake inhibitor, among other properties. Of the TCAs, noxiptiline has been described as one of the most effective, rivaling amitriptyline in clinical efficacy.

<span class="mw-page-title-main">Amitriptylinoxide</span> Chemical compound

Amitriptylinoxide, or amitriptyline N-oxide, is a tricyclic antidepressant (TCA) which was introduced in Europe in the 1970s for the treatment of depression.

<span class="mw-page-title-main">Imipraminoxide</span> Chemical compound

Imipraminoxide, or imipramine N-oxide, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1960s for the treatment of depression.

References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ↑ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN   3-88763-075-0.
  3. 1 2 3 4 5 6 Sittig M (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. ISBN   0-8155-1144-2.
  4. ↑ 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.
  5. ↑ "Novartis (dibenzepin) - Prescribing Information" (PDF).
  6. ↑ Paloucek FP, Leikin JB (2007). Poisoning and Toxicology Handbook, Fourth Edition (Poisoning and Toxicology Handbook (Leiken & Paloucek's)). Informa Healthcare. ISBN   978-1-4200-4479-9.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  10. 1 2 Barth N, Manns M, Muscholl E (1975). "Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart". Naunyn-Schmiedeberg's Arch. Pharmacol. 288 (2–3): 215–31. doi:10.1007/bf00500528. PMID   1161046. S2CID   11641400.
  11. 1 2 Hyttel J (1978). "Inhibition of [3H]dopamine accumulation in rat striatal synaptosomes by psychotropic drugs". Biochem. Pharmacol. 27 (7): 1063–8. doi:10.1016/0006-2952(78)90159-4. PMID   656154.
  12. 1 2 3 4 5 6 7 8 Closse A, Jaton AL (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. 326 (4): 291–3. doi:10.1007/bf00501432. PMID   6148707. S2CID   24925602.
  13. 1 2 3 4 5 6 Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R (2012). "Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Arch. Pharmacol. 385 (2): 145–70. doi:10.1007/s00210-011-0704-0. PMID   22033803. S2CID   14274150.
  14. 1 2 Rehavi M, Maayani S, Goldstein L, Assael M, Sokolovsky M (1977). "Antimuscarinic properties of antidepressants: dibenzepin (Noveril)". Psychopharmacology. 54 (1): 35–8. doi:10.1007/bf00426538. PMID   20647. S2CID   27031652.
  15. ↑ Rao ML, Frahnert C, Zagorski O (2002). "Initial serotonin transport into viable platelets and imipramine binding to platelet membranes". J Neural Transm (Vienna). 109 (5–6): 547–56. doi:10.1007/s007020200045. PMID   12111448. S2CID   9703461.
  16. ↑ Aldenhoff J (2007). "Medikamente und andere Behandlungsverfahren". Psychiatrische Therapie. Schattauer Verlag. pp. 270–. ISBN   978-3-7945-2189-0.
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