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			{{Short description|Antidepressant}}
			{{Distinguish|Doxepin}}
	{{Drugbox		{{Drugbox
			| Verifiedfields = changed
	| verifiedrevid = 447387602
			| Watchedfields = changed
	| IUPAC_name = (''E'',''Z'')-3-(dibenzothiepin-11(6''H'')-ylidene)-''N'',''N''-dimethylpropan-1-amine
			| verifiedrevid = 448788673
	| image = Dosulepin (cis,trans-mixture) Structural Formulae.png
			| IUPAC_name = (3''E'')-3-(6''H''-benzobenzothiepin-11-ylidene)-''N'',''N''-dimethylpropan-1-amine
			| image = Dosulepin2DACS2.svg
			| width = 200px
			| image2 = Dosulepin-from-HCl-1987-xtal-CCDC-1160822.png
			| width2 = 225px
			| USAN = dothiepin
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Prothiaden, others
	| Drugs.com = {{drugs.com|international|dosulepin}}		| Drugs.com = {{drugs.com|international|dosulepin}}
	| pregnancy_category = C		| pregnancy_AU = C
	| legal_status = Rx-only		| legal_AU = S4
	| routes_of_administration = Oral		| routes_of_administration = ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = 30%		| bioavailability = 30%<ref name="pmid2670509" />
			| protein_bound = 84%<ref name="TGA" />
	| metabolism = ]
			| metabolism = ] (N-], S-], ])<ref name="TGA" />
	| elimination_half-life = 20 hours
			| metabolites = Northiaden, dothiepin sulfoxide, northiaden sulfoxide, ] ]s<ref name="pmid2670509" />
	| excretion = ]
			| elimination_half-life = Dothiepin: 14.4–23.9 hours<ref name="pmid2670509" /><br />Dothiepin sulfoxide: 22.7–25.5 hours<ref name="pmid2670509" /><br />Northiaden: 34.7–45.7 hours<ref name="pmid2670509" /><br />Northiaden sulfoxide: 24.2–33.5 hours<ref name="pmid2670509" />
			| excretion = ]: 56%<ref name="pmid2670509" /><br />]: 15%<ref name="pmid2670509" />
	<!--Identifiers-->		<!--Identifiers-->
			| index2_label = HCl
	| CAS_number = 113-53-1
			| CAS_number_Ref = {{cascite|correct|CAS}}
	| ATC_prefix = N06
			| CAS_number =  113-53-1
	| ATC_suffix = AA16
			| CAS_number2_Ref = {{cascite|correct|CAS}}
	| PubChem = 13473
			| CAS_number2 = 897-15-4
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = W13O82Z7HL		| UNII = W13O82Z7HL
			| UNII2_Ref = {{fdacite|correct|FDA}}
			| UNII2 = 3H0042311V
			| DrugBank = DB09167
			| ATC_prefix = N06
			| ATC_suffix = AA16
			| PubChem = 5284550
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D07872		| KEGG = D07872
			| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 36803
			| ChEMBL_Ref = {{ebicite|changed|EBI}}
			| ChEMBL = 108947
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = 4447605
			| synonyms = IZ-914, KS-1596<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />
	<!--Chemical data-->		<!--Chemical data-->
	| C=19 | H=21 | N=1 | S=1		| C=19 | H=21 | N=1 | S=1
			| SMILES = CN(C)CC/C=C/1\C2=CC=CC=C2CSC3=CC=CC=C31
	| molecular_weight = 295.45 g/mol
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 1S/C19H21NS/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+
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = PHTUQLWOUWZIMZ-GZTJUZNOSA-N
	}}		}}
			'''Dosulepin''', also known as '''dothiepin''' and sold under the brand name '''Prothiaden''' among others, is a ] (TCA) which is used in the treatment of ].<ref name="pmid2670509">{{cite journal | vauthors = Lancaster SG, Gonzalez JP | title = Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness | journal = Drugs | volume = 38 | issue = 1 | pages = 123–47 | year = 1989 | pmid = 2670509 | doi = 10.2165/00003495-198938010-00005 }}</ref><ref name="pmid7846285">{{cite journal | vauthors = Donovan S, Dearden L, Richardson L | title = The tolerability of dothiepin: a review of clinical studies between 1963 and 1990 in over 13,000 depressed patients | journal = Prog. Neuropsychopharmacol. Biol. Psychiatry | volume = 18 | issue = 7 | pages = 1143–62 | year = 1994 | pmid = 7846285 | doi = 10.1016/0278-5846(94)90117-1| s2cid = 29749302 }}</ref><ref name="MD"/> Dosulepin was once the most frequently prescribed antidepressant in the ], but it is no longer widely used due to its relatively high ] in ] without therapeutic advantages over other TCAs.<ref name="pmid7846285"/><ref name="pmid16390222">{{cite journal | vauthors = Thanacoody HK, Thomas SH | title = Tricyclic antidepressant poisoning : cardiovascular toxicity | journal = Toxicol Rev | volume = 24 | issue = 3 | pages = 205–14 | year = 2005 | pmid = 16390222 | doi = 10.2165/00139709-200524030-00013| s2cid = 44532041 }}</ref><ref name="pmid17471183">{{cite journal | vauthors = Gillman PK | title = Tricyclic antidepressant pharmacology and therapeutic drug interactions updated | journal = Br. J. Pharmacol. | volume = 151 | issue = 6 | pages = 737–48 | year = 2007 | pmid = 17471183 | pmc = 2014120 | doi = 10.1038/sj.bjp.0707253 }}</ref> It acts as a ] (SNRI) and also has other activities including ], ], ], ], and ] effects.<ref name="pmid2670509" /><ref name="LemkeWilliams2012" /><ref name="HealCheetham1992" />
	'''Dosulepin''' (]), formerly known as '''dothiepin''' (]), is a ] (TCA). It is sold under the brand names '''Prothiaden''', '''Dothep''', '''Thaden''' and '''Dopress'''. Dosulepin blocks the ] of ] and ] in the brain, thereby increasing their levels. It is believed that this action is responsible for its mood-elevating effects.
	== Indications ==		==Medical uses==
			Dosulepin is used for the treatment of ].<ref name="pmid2670509" /><ref name="TGA">{{cite web|title=Dothep Dothiepin hydrochloride|work=TGA eBusiness Services|publisher=Alphapharm Pty Limited|date=1 November 2013|access-date=3 December 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04551-3|format=PDF}}</ref><ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref><ref name="BNF">{{cite book | isbn = 978-0-85711-084-8 | title = British National Formulary (BNF) | last1 = Joint Formulary Committee | year = 2013 | publisher = Pharmaceutical Press | location = London, UK | edition = 65 | url-access = registration | url = https://archive.org/details/bnf65britishnati0000unse }}</ref> There is clear evidence of the efficacy of dosulepin in ], though the drug may be needed for up to a year.<ref>{{cite journal | vauthors = Feinmann C, Harris M, Cawley R | title = Psychogenic facial pain: presentation and treatment | journal = British Medical Journal | volume = 288 | issue = 6415 | pages = 436–438 | date = February 1984 | pmid = 6419955 | pmc = 1444752 | doi = 10.1136/bmj.288.6415.436 }}</ref>
			==Contraindications==
	Dosulepin is relatively mild and is used for low-level anxiety, depression and similar disorders, as well as the treatment of chronic and ongoing pain disorders, particularly where insomnia and/or loss of appetite are present. It can take between two and four weeks of regular usage to become effective; it is often started at a low level and the dosage increased if this is ineffective. The drug causes drowsiness as a side-effect, and this may be used as part of the treatment, since anxiety-depressive patients may have difficulty sleeping; it can also be combined with other drugs such as ]. The drug is also an effective preventative for ].
			Contraindications include:<ref name="TGA" />
			* ] as it can lower the seizure threshold
	== Dosage ==
			* TCAs should not be used concomitantly or within 14 days of treatment with monoamine oxidase inhibitors due to the risk for ]
			* Acute recovery phase following ] as TCAs may produce conduction defects and arrhythmias
			* ]
			* Hypersensitivity to dosulepin
			==Side effects==
	Adults: Initially 75 mg/day in divided doses or as a single dose at night, increasing to 150 mg/day. In certain circumstances, e.g. in hospital use or unresponsive patients, dosages up to 300 mg daily have been used.
			'''Common adverse effects:'''<ref name="TGA" />
			{{div col|colwidth=18em}}
	Suggested regimens: 25 or 50 mg three times daily or, alternatively, 75 or 150 mg as a single dose at night. Should the regimen of 150 mg as a single night-time dose be adopted, it is better to give a smaller dose for the first few days.
			* Drowsiness
			* ]
	Elderly: 50 to 75 mg daily initially. As with any antidepressant, the initial dose should be increased with caution under close supervision. Half the normal adult dose may be sufficient to produce a satisfactory clinical response.
			* Tremor
			*
	Children: Not recommended.
			* Disorientation
	<ref></ref>
			* Dizziness
			* ]s
	== Side effects ==
			* Alterations to ] patterns
			* Dry mouth
	The most common side effects are drowsiness and dry mouth as well as dry eyes. Other less common side effects may include:
			* Sweating
	* ]
	* ]
	* ]
	* ]		* ]
			* Hypotension
	* ]s, especially of the hands
			* Postural hypotension
	* Blood disorders
			* Tachycardia
	* ]
			* Palpitations
	* ]
			* Arrhythmias
	* ]
			* Conduction defects
	* Increased ] and increased vulnerability to sunburn
			* Increased or decreased libido
	These side effects cease when treatment ceases. Alcohol should be avoided whilst taking dosulepin as it may increase some side-effects.
	Whilst dosulepin is not addictive, it should not be stopped suddenly as there is a risk of initial withdrawal symptoms which may be mistaken for some of the original indications for the drug:
	* Nausea		* Nausea
	* Vomiting		* Vomiting
			* Constipation
	* Loss of appetite
			* Blurred vision
	* Headache
			{{div col end}}
	* Giddiness
	* Chills
			'''Less common adverse effects:'''<ref name="TGA" />
	* Insomnia
			{{div col|colwidth=22em}}
			* Disturbed concentration
			* ]
			* ]
	* Anxiety		* Anxiety
			* Fatigue
			* Headaches
			* Restlessness
			* Excitement
			* Insomnia
			* ]
			* Nightmares
			* ]
			* ]
			* Incoordination
			* Seizures
			* Paralytic ]
			* Hypertension
			* Heart block
			* ]
			* Stroke
			* ] (swelling of breast tissue in males)
			* Testicular swelling
			* Impotence
			* Epigastric distress
			* Abdominal cramps
			* Parotid swellings
			* Diarrhea
			* ] (swelling of the mouth)
			* Black tongue
			* Peculiar taste sensations
			* Cholestatic ]
			* Altered liver function
			* ] (swelling of the liver)
			* Skin rash
			* Urticaria (hives)
			* Photosensitisation
			* Skin blisters
			* Angioneurotic edema
			* Weight loss
			* Urinary frequency
			* Mydriasis
			* Weight gain
			* ] (low blood sodium)
			* Movement disorders
			* ] (indigestion)
			* Increased intraocular pressure
			* Changes in blood sugar levels
			{{div col end}}
			* ] (an abnormally low number of ] in the blood. This makes one more susceptible to bleeds)
			* ] (an abnormally high number of eosinophils in the blood)
			* ] (a dangerously low number of white blood cells in the blood leaving one open to potentially life-threatening infections)
			* ] (lactation that is unassociated with breastfeeding and lactation)
			==Overdose==
	== Contraindications ==
			{{Main|Tricyclic antidepressant overdose}}
			The symptoms and the treatment of an overdose are largely the same as for the other TCAs.<ref name = AMH/> Dosulepin may be particularly toxic in overdose compared to other TCAs.<ref name = AMH/> The onset of toxic effects is around 4–6 hours after dosulepin is ingested.<ref name="TGA" /> In order to minimise the risk of overdose it is advised that patients only receive a limited number of tablets at a time so as to limit their risk of overdosing.<ref name="TGA" /> It is also advised that patients are not prescribed any medications that are known to increase the risk of toxicity in those receiving dosulepin due to the potential for mixed overdoses.<ref name="TGA" /> The medication should also be kept out of reach of children.<ref name="TGA" />
	Contra indications include:
			==Interactions==
	* Certain conditions of the heart, mainly those affecting the electrical impulses to the heart muscle, particularly ] or recent ]
			Dosulepin can potentiate the effects of ] and at least one death has been attributed to this combination.<ref name="TGA" /> TCAs potentiate the sedative effects of barbiturates, tranquilizers and {{abbrlink|CNS|central nervous system}} ]s.<ref name="TGA" /> ] and other adrenergic neuron blocking drugs can have their antihypertensive effects blocked by dosulepin.<ref name="TGA" /> Sympathomimetics may potentiate the sympathomimetic effects of dosulepin.<ref name="TGA" /> Due to the anticholinergic and antihistamine effects of dosulepin anticholinergic and antihistamine medications may have their effects potentiated by dosulepin and hence these combinations are advised against.<ref name="TGA" /> Dosulepin may have its postural hypotensive effects potentiated by ].<ref name="TGA" /> Anticonvulsants may have their efficacy reduced by dosulepin due to its ability to reduce the seizure threshold.<ref name="TGA" />
	* ].
	* ] or ]
	* ], ], ] or ]
	* ], vulnerability to dizziness or fainting
	* History of ] or ]
			==Pharmacology==
	== Drug interactions ==
			===Pharmacodynamics===
	The drug can interact dangerously with ]s and should not be taken in combination with ] or ] in particular.
			{{See also|Pharmacology of antidepressants|Tricyclic antidepressant#Binding profiles}}
			{| class="wikitable sortable floatright" style="font-size:small;"
			|+ Dosulepin (and metabolite)<ref name="PDSP">{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | author1-link=Bryan Roth | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=dothiepin&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref>
			|-
			! Site !! {{abbr|DSP|Dosulepin}} !! {{abbrlink|NTD|Northiaden}} !! Species !! Ref
			|-
			| '''{{abbrlink|SERT|Serotonin transporter}}''' || '''8.6–78''' || '''192''' || '''Human/rat''' || <ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–258 | date = December 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9 }}</ref><ref name="HealCheetham1992">{{cite journal| vauthors = Heal D, Cheetham S, Martin K, Browning J, Luscombe G, Buckett R |title=Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs|journal=Drug Development Research|volume=27|issue=2|year=1992|pages=121–135|issn=0272-4391|doi=10.1002/ddr.430270205|s2cid=95382318}}</ref>
			|-
			| '''{{abbrlink|NET|Norepinephrine transporter}}''' || '''46–70''' || '''25''' || '''Human/rat''' || <ref name="pmid9537821" /><ref name="HealCheetham1992" />
			|-
			| {{abbrlink|DAT|Dopamine transporter}} || 5,310 || 2,539 || Human/rat || <ref name="pmid9537821" /><ref name="HealCheetham1992" />
			|-
			| ] || 4,004 || 2,623 || Rat || <ref name="pmid10379421">{{cite journal |vauthors=Sánchez C, Hyttel J |title=Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding |journal=Cell. Mol. Neurobiol. |volume=19 |issue=4 |pages=467–89 |year=1999 |pmid=10379421 |doi= 10.1023/A:1006986824213|s2cid=19490821 }}</ref>
			|-
			| ''']''' || '''152''' || '''141''' || '''Rat''' || <ref name="HealCheetham1992" />
			|-
			| ] || 419 || 950 || Rat || <ref name="HealCheetham1992" />
			|-
			| ] || 2,400 || {{abbr|ND|No data}} || Human || <ref name="pmid6086881">{{cite journal | vauthors = Richelson E, Nelson A | title = Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro | journal = J. Pharmacol. Exp. Ther. | volume = 230 | issue = 1 | pages = 94–102 | year = 1984 | pmid = 6086881 }}</ref>
			|-
			| ''']''' || '''3.6–4''' || '''25''' || '''Human/rat''' || <ref name="HealCheetham1992" /><ref name="pmid6086881" />
			|-
			| '''{{abbrlink|mACh|Muscarinic acetylcholine receptor}}''' || '''25–26''' || '''110''' || '''Human/rat''' || <ref name="HealCheetham1992" /><ref name="pmid7855217">{{cite journal | vauthors = Cusack B, Nelson A, Richelson E | title = Binding of antidepressants to human brain receptors: focus on newer generation compounds | journal = Psychopharmacology | volume = 114 | issue = 4 | pages = 559–65 | year = 1994 | pmid = 7855217 | doi = 10.1007/bf02244985| s2cid = 21236268 }}</ref>
			|-
			| '''&nbsp;&nbsp;]''' || '''18''' || '''{{abbr|ND|No data}}''' || '''Human''' || <ref name="pmid8100134">{{cite journal |vauthors=Stanton T, Bolden-Watson C, Cusack B, Richelson E |title=Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics |journal=Biochem. Pharmacol. |volume=45 |issue=11 |pages=2352–4 |year=1993 |pmid=8100134 |doi= 10.1016/0006-2952(93)90211-e}}</ref>
			|-
			| '''&nbsp;&nbsp;]''' || '''109''' || '''{{abbr|ND|No data}}''' || '''Human''' || <ref name="pmid8100134" />
			|-
			| '''&nbsp;&nbsp;]''' || '''38''' || '''{{abbr|ND|No data}}''' || '''Human''' || <ref name="pmid8100134" />
			|-
			| '''&nbsp;&nbsp;]''' || '''61''' || '''{{abbr|ND|No data}}''' || '''Human''' || <ref name="pmid8100134" />
			|-
			| '''&nbsp;&nbsp;]''' || '''92''' || '''{{abbr|ND|No data}}''' || '''Human''' || <ref name="pmid8100134" />
			|- class="sortbottom"
			| colspan="5" style="width: 1px;" | Values are K<sub>i</sub> (nM). The smaller the value, the more strongly the drug binds to the site.
			|}
			Dosulepin is a ] of the ] (SERT) and the ] (NET), thereby acting as an SNRI.<ref name="HealCheetham1992" /><ref name="LemkeWilliams2012" /> It is also an ] of the ] ], ], ] ]s, and ]s (mACh), as well as a ] of ]s (VGSCs).<ref name="HealCheetham1992" /><ref name="pmid2670509" /> The antidepressant effects of dosulepin are thought to be due to ] of the ] of ] and possibly also of serotonin.<ref name="pmid2670509" />
	The sedative effects of other CNS depressants (benzodiazepines such as diazepam and lorazepam, sedative antihistamines, opiates, etc.) may be increased.
			Dosulepin has three ], northiaden (desmethyldosulepin), dosulepin sulfoxide, and northiaden sulfoxide, which have longer ] than that of dosulepin itself.<ref name="HealCheetham1992" /> However, whereas northiaden has potent activity similarly to dosulepin, the two sulfoxide metabolites have dramatically reduced activity.<ref name="HealCheetham1992" /> They have been described as essentially inactive, and are considered unlikely to contribute to either the therapeutic effects or side effects of dosulepin.<ref name="HealCheetham1992" /> Relative to dosulepin, northiaden has reduced activity as a ], ], and ] and greater potency as a ],<ref name="HealCheetham1992" /> similarly to other ] TCAs.<ref name="HalesYudofsky2011">{{cite book| vauthors = Hales RE, Yudofsky SC, Gabbard GO |title=Essentials of Psychiatry|url=https://books.google.com/books?id=Hf50vMMMv_wC&pg=PA468|year=2011|publisher=American Psychiatric Pub|isbn=978-1-58562-933-6|pages=468–}}</ref><ref name="BurtisAshwood2012">{{cite book| vauthors = Burtis CA, Ashwood ER, Bruns DE |title=Tietz Textbook of Clinical Chemistry and Molecular Diagnostics - E-Book|url=https://books.google.com/books?id=BBLRUI4aHhkC&pg=PA1129|date=14 October 2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-5942-2|pages=1129–}}</ref> Unlike the sulfoxide metabolites, northiaden is thought to play an important role in the effects of dosulepin.<ref name="HealCheetham1992" />
	This drug should not be started within 2 weeks of stopping a ] (MAOI) antidepressant, and should not be co-administered with any selective ] (SSRI) antidepressant such as ]), or any medication which affects the electrical impulses to the heart (e.g. ], ] or ]).
			Although Heal & Cheetham (1992) reported relatively high K<sub>i</sub> values of 12 and 15&nbsp;nM for dosulepin and northiaden at the rat α<sub>2</sub>-adrenergic receptor and suggested that antagonism of the receptor could be involved in the antidepressant effects of dosulepin,<ref name="HealCheetham1992" /> Richelson & Nelson (1984) found a low K<sub>D</sub> of only 2,400&nbsp;nM for dosulepin at this receptor using human brain tissue.<ref name="pmid6086881" /> This suggests that it in fact has low potency for this action, similarly to other TCAs.<ref name="pmid6086881" />
	The drug is not recommended for use by children nor to be taken in combination with some other drugs, including herbal remedies.
			===Pharmacokinetics===
	== Overdose ==
			Dosulepin is readily absorbed from the small intestine and is extensively metabolized on first-pass through the liver into its chief active metabolite, northiaden.<ref name="TGA" /> Peak plasma concentrations of between 30.4 and 279&nbsp;ng/mL (103–944&nbsp;nmol/L) occur within 2–3 hours of oral administration.<ref name="TGA" /> It is distributed in breast milk and crosses the placenta and ].<ref name="TGA" /> It is highly bound to plasma proteins (84%), and has a whole-body ] of 51&nbsp;hours.<ref name="TGA" />
	{{main|Tricyclic antidepressant overdose}}
	The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants.
	==Chemistry==		==Chemistry==
			Dosulepin is a ], specifically a ], and possesses three ]s fused together with a ] attached in its ].<ref name="Aronson2009">{{cite book| vauthors = Aronson JK |title=Meyler's Side Effects of Psychiatric Drugs|url=https://books.google.com/books?id=AmYFTSO8jCkC&pg=PA7|year=2009|publisher=Elsevier|isbn=978-0-444-53266-4|pages=7–}}</ref> It is the only TCA with a dibenzothiepine ] to have been marketed.<ref name="Aronson2009" /><ref name="Ritsner2013">{{cite book| vauthors = Ritsner MS |title=Polypharmacy in Psychiatry Practice, Volume I: Multiple Medication Use Strategies|url=https://books.google.com/books?id=jy-LMZU7338C&pg=PA270|date=15 February 2013|publisher=Springer Science & Business Media|isbn=978-94-007-5805-6|pages=270–271}}</ref> The drug is a ] TCA, with its ]-] metabolite northiaden (desmethyldosulepin) being a ].<ref name="CutlerSramek1994">{{cite book| vauthors = Cutler NR, Sramek JJ, Narang PK |title=Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology|url=https://books.google.com/books?id=ncRXa8Dq88QC&pg=PA160|date=20 September 1994|publisher=John Wiley & Sons|isbn=978-0-471-95052-3|pages=160–}}</ref><ref name="AnzenbacherZanger2012">{{cite book| vauthors = Anzenbacher P, Zanger UM |title=Metabolism of Drugs and Other Xenobiotics|url=https://books.google.com/books?id=f-XHh17NfwgC&pg=PA302|date=23 February 2012|publisher=John Wiley & Sons|isbn=978-3-527-64632-6|pages=302–}}</ref> Other tertiary amine TCAs include ], ], ], ], and ].<ref name="Anthony2002">{{cite book| vauthors = Anthony PK |title=Pharmacology Secrets|url=https://books.google.com/books?id=_QQsj3PAUrEC&pg=PA39|year=2002|publisher=Elsevier Health Sciences|isbn=1-56053-470-2|pages=39–}}</ref><ref name="CowenHarrison2012">{{cite book| vauthors = Cowen P, Harrison P, Burns T |title=Shorter Oxford Textbook of Psychiatry|url=https://books.google.com/books?id=Y1DtSGq-LnoC&pg=PA532|date=9 August 2012|publisher=OUP Oxford|isbn=978-0-19-162675-3|pages=532–}}</ref> Dosulepin exhibits ] ] like ] but in contrast the pure ''E'' or ''trans'' isomer is used medicinally.<ref name="Elks2014" /><ref name="LemkeWilliams2012">{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA607|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=607–}}</ref><ref name="Springer2012">{{cite book|title=Psychotropic Agents: Part I: Antipsychotics and Antidepressants|url=https://books.google.com/books?id=oK7tCAAAQBAJ&pg=PA354|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-67538-6|pages=354–}}</ref> The drug is used commercially as the ] ]; the free base is not used.
	Dosulepin is made as follows:
	]
			==History==
	Zirkle, C. L.; 1971, {{US Patent|3609167}}.
			Dosulepin was developed by SPOFA.<ref name="pmid19557250">{{cite journal | vauthors = Andersen J, Kristensen AS, Bang-Andersen B, Strømgaard K | title = Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters | journal = Chem. Commun. | issue = 25 | pages = 3677–92 | year = 2009 | pmid = 19557250 | doi = 10.1039/b903035m }}</ref> It was patented in 1962 and first appeared in the literature in 1962.<ref name="pmid19557250" /> The drug was first introduced for medical use in 1969, in the ].<ref name="pmid19557250" /><ref name="Dart2004">{{cite book| vauthors = Dart RC |title=Medical Toxicology|url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA836|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2845-4|pages=836–}}</ref>
			==Society and culture==
	Dosulepin is also the dibenzothiepine analogue of ], from which it differs by the replacement of the oxygen position with that of sulfur.
	== See also ==		===Generic names===
			''Dosulepin'' is the ] and ] ] of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while ''dosulepin hydrochloride'' is its {{abbrlink|BANM|British Approved Name}} and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014">{{cite book | vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA468|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=468–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA369|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=369–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA105|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=105–}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/dosulepin.html|title = Dosulepin}}</ref> ''Dothiepin'' is the former {{abbrlink|BAN|British Approved Name}} of the drug while ''dothiepin hydrochloride'' is the former {{abbrlink|BANM|British Approved Name}} and remains the current {{abbrlink|USAN|United States Adopted Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" /> Its generic name in ] and ] and its {{abbrlink|DCIT|Denominazione Comune Italiana}} are ''dosulepina'', in ] and its {{abbrlink|DCF|Dénomination Commune Française}} are ''dosulépine'', and in ] is ''dosulepinum''.<ref name="IndexNominum2000" /><ref name="Drugs.com" />
	* ]
	== References ==		===Brand names===
			Dosulepin is marketed throughout the world mainly under the brand name Prothiaden.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is or has been marketed under a variety of other brand names as well, including Altapin, Depresym, Dopress, Dothapax, Dothep, Idom, Prepadine, Protiaden, Protiadene, Thaden, and Xerenal.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />
	{{Reflist|2}}
	{{Refimprove|date=February 2010}}
			===Availability===
			Dosulepin is marketed throughout ] (as Prothiaden, Protiaden, and Protiadene), ] (as Dothep and Prothiaden), ] (as Dopress) and ] (as Thaden).<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="MD">{{cite book|title=Dosulepin Hydrochloride|work=Martindale: The Complete Drug Reference|date=5 December 2011|access-date=15 August 2017|url=http://www.medicinescomplete.com/mc/martindale/current/2512-p.htm|publisher=Pharmaceutical Press|location=London, UK}}</ref><ref name="AMH"/><ref name="BNF"/> It is also available in ], ], ], ], ], and ].<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="MD" /> The drug is not available in the ] or ].<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="MD" />
			==References==
			{{Reflist|2}}
	{{Antidepressants}}		{{Antidepressants}}
			{{Neuropathic pain and fibromyalgia pharmacotherapies}}
	{{Anxiolytics}}
			{{Navboxes
	{{Adrenergics}}
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	{{Cholinergics}}
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	{{Histaminergics}}
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	{{Serotonergics}}
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	{{Tricyclics}}		{{Tricyclics}}
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