View source for Captodiame

{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 447821290
| IUPAC_name = 2-[(4-butylsulfanylphenyl)-phenyl-methyl]sulfanyl-''N'',''N''-dimethylethanamine
| image = Captodiame.svg
| image_class = skin-invert-image

<!--Clinical data-->
| tradename =  
| Drugs.com = {{drugs.com|international|captodiame}}
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = <!--             / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_NZ = <!-- Class A, B, C -->
| legal_UK = <!-- GSL         / P       / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                   / Rx-only  / Schedule I, II, III, IV, V -->
| legal_EU = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_status = Rx-only
| routes_of_administration = Oral

<!--Pharmacokinetic data-->
| excretion = [[Kidney|Renal]]

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 486-17-9
| ATC_prefix = N05
| ATC_suffix = BB02
| PubChem = 10240
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB09014
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9823
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = H93K9455DD
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07316

<!--Chemical data-->
| C=21 | H=29 | N=1 | S=2 
| smiles = S(c1ccc(cc1)C(SCCN(C)C)c2ccccc2)CCCC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H29NS2/c1-4-5-16-23-20-13-11-19(12-14-20)21(24-17-15-22(2)3)18-9-7-6-8-10-18/h6-14,21H,4-5,15-17H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IZLPZXSZLLELBJ-UHFFFAOYSA-N
}}

'''Captodiame''' ([[International Nonproprietary Name|INN]]), also known as '''captodiamine''', is an [[antihistamine]] sold under the trade names '''Covatine''', '''Covatix''', and '''Suvren''' which is used as a [[sedative]] and [[anxiolytic]]. The structure is related to [[diphenhydramine]].<ref name=Mercier-Guyon/>

A 2004 study suggested captodiame may be helpful in preventing [[benzodiazepine withdrawal syndrome]] in people discontinuing [[benzodiazepine]] treatment.<ref name=Mercier-Guyon>{{cite journal |vauthors=Mercier-Guyon C, Chabannes JP, Saviuc P |title=The role of captodiamine in the withdrawal from long-term benzodiazepine treatment |journal=Curr Med Res Opin |volume=20 |issue=9 |pages=1347–55 |year=2004 |pmid=15383182 |doi=10.1185/030079904125004457|s2cid=32561767 }} [http://www.medscape.com/viewarticle/489359 Free full text with registration]</ref>

In addition to its actions as an antihistamine, captodiamine has been found to act as a [[5-HT2C receptor|5-HT<sub>2C</sub> receptor]] [[receptor antagonist|antagonist]] and [[sigma-1 receptor|σ<sub>1</sub> receptor]] and [[D3 receptor|D<sub>3</sub> receptor]] [[agonist]].<ref name="pmid23863923">{{cite journal | vauthors = Ring RM, Regan CM | title = Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism | journal = J. Psychopharmacol. (Oxford) | volume = 27 | issue = 10 | pages = 930–9 |date=October 2013  | pmid = 23863923 | doi = 10.1177/0269881113497614 | hdl = 10197/4383 | hdl-access = free }}</ref> It produces [[antidepressant]]-like effects in rats.<ref name="pmid23863923" /> However, captodiamine is unique among antidepressant-like drugs in that it increases [[brain-derived neurotrophic factor]] (BDNF) levels in the [[hypothalamus]] but not in the [[frontal cortex]] or [[hippocampus]].<ref name="pmid23863923" /> This unique action may be related to its ability to attenuate [[Stress (psychology)|stress]]-induced [[anhedonia]] and [[corticotropin-releasing factor]] (CRF) signaling in the hypothalamus.<ref name="pmid23863923" />

==Synthesis==
The oxygen atom in these molecules can in many cases be dispensed with as well; substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. 
[[File:Captodiamine synthesis.png|class=skin-invert-image|thumb|center|700px|Captodiamine synthesis: Hubner Oluf Herman, Petersen Povl Viggo. {{US patent|2830088}} (1958).]]
[[Friedel-Crafts]] acylation of the n-butyl ether of thiophenol with [[benzoyl chloride]] gives the corresponding [[benzophenone]]. Reduction of the ketone with zinc/NaOH followed by treatment with HCl in ether affords the benzhydryl chloride. Displacement of the halogen with [[thiourea]] gives, by reaction of the last at its most nucleophilic center, the [[isothiouronium]] salt. Hydrolysis of the salt leads to the sulfur analog of a benzhydrol. Alkylation of the sodium salt of this last with ''N''-(2-chloroethyl)dimethylamine affords captodiame.

==See also==
* [[Hydroxyzine]]
* [[Cyproheptadine]]

==References==
{{Reflist}}

{{Sedatives}}
{{Anxiolytics}}
{{Navboxes
| title = [[Pharmacodynamics]]
| titlestyle = background:#ccccff
| list1 = 
{{Dopamine receptor modulators}}
{{Histamine receptor modulators}}
{{Muscarinic acetylcholine receptor modulators}}
{{Serotonin receptor modulators}}
{{Sigma receptor modulators}}
}}

[[Category:5-HT2C antagonists]]
[[Category:Antihistamines]]
[[Category:Anxiolytics]]
[[Category:Dopamine agonists]]
[[Category:H1 receptor antagonists]]
[[Category:Muscarinic antagonists]]
[[Category:Sedatives]]
[[Category:Sigma agonists]]
[[Category:Thioethers]]