The ketone dibenzosuberenone (1) is treated with hydroxylamine (2) to give its ketoxime (3). Base-catalyzed alkylation with ClCH2CH2N(CH3)2 (4) yields noxiptiline.[10][11][12]
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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.
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.
Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat major depressive disorder, and 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.
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.
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, sold under the brand name Aventyl, among others, is a tricyclic antidepressant. 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.
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.
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, 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.
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.
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.
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, 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.
Melitracen is a tricyclic antidepressant (TCA), for the treatment of depression and anxiety. In addition to single drug preparations, it is also available as Deanxit, marketed by Lundbeck, a combination product containing both melitracen and flupentixol.
Quinupramine is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression.
Demexiptiline is a tricyclic antidepressant (TCA) used in France for the treatment of depression. It acts primarily as a norepinephrine reuptake inhibitor similarly to desipramine.
Amitriptylinoxide, or amitriptyline N-oxide, is a tricyclic antidepressant (TCA) which was introduced in Europe in the 1970s for the treatment of depression.
Imipraminoxide, or imipramine N-oxide, is a tricyclic antidepressant (TCA) that was introduced in Europe in the 1960s for the treatment of depression.
Cyanodothiepin (developmental code name BTS-56424) is a tricyclic antidepressant (TCA) acting as a potent and highly selective (over norepinephrine and dopamine uptake) inhibitor of the reuptake of serotonin that was never marketed. It also has moderate affinity for the muscarinic acetylcholine receptors and weak/negligible affinity for the α1-adrenergic, 5-HT2A, D1, and D2 receptors; the H1 receptor has not been assayed, but cyanodothiepin is less sedating than the related drug cianopramine, suggesting that its antihistamine activity is not as pronounced as other TCAs. Cyanodothiepin is active in the forced swimming test (FST), implying that it may possess antidepressant properties in humans. However, it is only weakly active compared to cianopramine and imipramine in monoamine depletion-based tests of antidepressant potential.
↑ 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 Archives of Pharmacology. 288 (2–3): 215–231. doi:10.1007/BF00500528. PMID1161046. S2CID11641400.
↑ 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): 13–18. PMID1687987.
↑ Lingjaerde O, Asker T, Bugge A, Engstrand E, Eide A, Grinaker H, etal. (January 1975). "Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline". Pharmakopsychiatrie, Neuro-Psychopharmakologie. 8 (1): 26–35. doi:10.1055/s-0028-1094440. PMID788000. S2CID44886111.
↑ Aichinger G, Behner O, Hoffmeister F, Schütz S (June 1969). "Basic tricyclic oxyiminoethers and their pharmacological properties". Arzneimittel-Forschung (in German). 19: Suppl 5a:838+. PMID5819763.
↑ US 3963778,Schütz S, Behner O, Hoffmeister F,"Basic oximes and their preparation",issued 1976-06-15, assigned to Bayer AG
↑ Wylie BB, Isaacson EI, Delgado JN (September 1965). "Synthesis of oxime esters and ethers as potential psychotropic agents". Journal of Pharmaceutical Sciences. 54 (9): 1373–1376. doi:10.1002/jps.2600540932. PMID5881239.
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