Cidoxepin

Last updated
Cidoxepin
Cidoxepin.svg
Clinical data
Other names(Z)-Doxepin; cis-Doxepin; P-4599
Identifiers
  • (3Z)-3-(6H-Benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
Chemical and physical data
Formula C19H21NO
Molar mass 279.383 g·mol−1
3D model (JSmol)
  • CN(C)CC/C=C\1/C2=CC=CC=C2COC3=CC=CC=C31
  • InChI=1S/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11-
  • Key:ODQWQRRAPPTVAG-BOPFTXTBSA-N

Cidoxepin (former developmental code name P-4599), also known as cis-doxepin or (Z)-doxepin, is a tricyclic antidepressant which was developed in the 1960s but was never marketed. [1] [2] It is the cis or (Z) stereoisomer of doxepin, a mixture of (E) and (Z) isomers that is used commercially in a ratio of approximately 85:15 with cidoxepin as a relatively minor constituent. [1] [3] However, the drug has similar activity to that of doxepin, acting as a serotonin–norepinephrine reuptake inhibitor, H1 receptor antagonist, and anticholinergic, and notably is thought to have more antidepressant activity than trans-doxepin. [3] [4] [5] The central anticholinergic activity of cidoxepin has been reported to be 3-fold greater than that of the trans isomer in mice. [5]

Contents

Cidoxepin has recently been reinvestigated and is now currently under development as an antihistamine by Elorac, Inc. for the treatment of chronic urticaria (hives). [4] As of 2017, it is in phase II clinical trials for this indication. [4] The drug was also under investigation for the treatment of allergic rhinitis (hay fever), atopic dermatitis (atopic eczema), and contact dermatitis, but development for these indications was discontinued. [4]

See also

Related Research Articles

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Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRI. 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.

Maprotiline

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 other secondary amine TCAs like nortriptyline and protriptyline, and has similar effects to them.

Hydroxyzine Antihistamine drug

Hydroxyzine, sold under the brand names Atarax and others, is an antihistamine medication. It is used in the treatment of itchiness, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.

Cetirizine Antihistamine medication

Cetirizine, sold under the brand name Zyrtec among others, is a second-generation antihistamine used to treat allergic rhinitis, dermatitis, and urticaria (hives). It is taken by mouth. Effects generally begin within an hour and last for about a day. The degree of benefit is similar to other antihistamines such as diphenhydramine.

Imipramine 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. The drug is also used to treat bedwetting. Imipramine is taken by mouth.

Desipramine 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.

Nortriptyline Antidepressant medication

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression, 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.

Doxepin

Doxepin is a medication used to treat major depressive disorder, anxiety disorders, chronic hives, and trouble sleeping. 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.

Tiotixene

Tiotixene, or thiothixene, sold under the brand name Navane among others, is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania. It was introduced in the United States in 1967 by Pfizer.

Trimipramine 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.

Dosulepin 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.

Mianserin Antidepressant

Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant which is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closely related to mirtazapine, both chemically and in terms of its actions and effects, although there are significant differences between the two drugs.

Butriptyline

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.

Lofepramine

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.

Iprindole

Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant (TCA) that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed. It was developed by Wyeth and was marketed in 1967. The drug has been described by some as the first "second-generation" antidepressant to be introduced. However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.

Opipramol σ1 receptor agonist used to treat depressive and anxiety disorders

Opipramol, sold under the brand name Insidon among others, is an anxiolytic and 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 sigma receptor agonist. It was developed by Schindler and Blattner in 1961.

Clopenthixol

Clopenthixol (Sordinol), also known as clopentixol, is a typical antipsychotic drug of the thioxanthene class. It was introduced by Lundbeck in 1961.

Bisulepin

Bisulepin is strong and relatively selective antihistamine (H1 antagonist) with hypnotic, antiadrenergic and very weak anticholinergic and antiserotonergic effects. Bisulepin is marketed in the Czech Republic and Slovakia under the trademark Dithiaden as tablets and injections.

Amesergide

Amesergide is a serotonin receptor antagonist of the ergoline and lysergamide families related to methysergide which was under development by Eli Lilly and Company for the treatment of a variety of conditions including depression, anxiety, schizophrenia, male sexual dysfunction, migraine, and thrombosis but was never marketed. It reached phase II clinical trials for the treatment of depression, erectile dysfunction, and premature ejaculation prior to the discontinuation of its development.

Nordoxepin

Nordoxepin, also known as N-desmethyldoxepin, is the major active metabolite of the tricyclic antidepressant (TCA) doxepin (Sinequan). It has been found to play a significant role in the antidepressant effects of doxepin.

References

  1. 1 2 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 469–. ISBN   978-1-4757-2085-3.
  2. Gallant DM, Bishop MP, Guerrero-Figueroa R, Selby M, Phillips R (1969). "Doxepin versus diazepam: a controlled evaluation in 100 chronic alcoholic patients". J Clin Pharmacol J New Drugs. 9 (1): 57–65. PMID   4885966.
  3. 1 2 Shufeng Zhou (6 April 2016). Cytochrome P450 2D6: Structure, Function, Regulation and Polymorphism. CRC Press. pp. 142–. ISBN   978-1-4665-9788-4.
  4. 1 2 3 4 "Cidoxepin - AdisInsight".
  5. 1 2 Hagedorn HW, Meiser H, Zankl H, Schulz R (2001). "Elimination of doxepin isomers from the horse following intravenous application". J. Vet. Pharmacol. Ther. 24 (4): 283–9. doi:10.1046/j.1365-2885.2001.00345.x. PMID   11555184.