Chemistry:Clorotepine

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Short description: Antipsychotic medication
Clorotepine
Clorotepine.svg
Clinical data
Trade namesClotepin, Clopiben
Other namesOctoclothepin; Octoclothepine; VUFB-6281; VUFB-10030
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC19H21ClN2S
Molar mass344.90 g·mol−1
3D model (JSmol)

Clorotepine (INN; brand names Clotepin, Clopiben), also known as octoclothepin or octoclothepine, is an antipsychotic of the tricyclic group which was derived from perathiepin in 1965 and marketed in the Czech Republic by Spofa in or around 1971 for the treatment of schizophrenic psychosis.[1][2][3][4][5][6]

Clorotepine is known to have high affinity for the dopamine D1,[7] D2,[8] D3,[8] and D4 receptors,[8] the serotonin 5-HT2A,[7] 5-HT2B,[9] 5-HT2C,[9] 5-HT6,[10] and 5-HT7 receptors,[10] the α1A-,[11] α1B-,[11] and α1D-adrenergic receptors,[11] and the histamine H1 receptors,[12] where it has been it has been confirmed to act as an antagonist (or inverse agonist) at most sites (and likely is as such at all of them based on structure–activity relationships), and it also blocks the reuptake of norepinephrine via inhibition of the norepinephrine transporter.[13]

Due to its very potent activity at the D2 receptor, along with tefludazine, clorotepine was used as the basis for developing a 3-dimensional (3D) pharmacophore for D2 receptor antagonists.[14]

See also

References

  1. ↑ Index nominum 2000: international drug directory. Taylor & Francis US. 2000. pp. 265. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA265. Retrieved 26 November 2011. 
  2. ↑ Dictionary of pharmacological agents. CRC Press. 1997. pp. 500. ISBN 978-0-412-46630-4. https://books.google.com/books?id=DeX7jgInYFMC&pg=PA500. Retrieved 26 November 2011. 
  3. ↑ "Pharmacological properties of a potent neuroleptic drug octoclothepin". Acta Biologica et Medica Germanica 39 (6): 723–40. 1980. PMID 6893891. 
  4. ↑ Annual Reports in Medicinal Chemistry. Academic Press. 1 January 1971. pp. 5. ISBN 978-0-12-040506-0. https://books.google.com/books?id=dBGM4WSV_YEC&pg=PA5. Retrieved 26 November 2011. 
  5. ↑ "ChemInform Abstract: Fifty Years in Chemical Drug Research". ChemInform 23 (9): no. 2010. doi:10.1002/chin.199209338. ISSN 0931-7597. 
  6. ↑ "[Clotepin]" (in cs). Cas. Lek. Cesk. 110 (17): 404–5. 1971. PMID 5576292. 
  7. ↑ 7.0 7.1 "Pyrrolo[1,3]benzothiazepine-based atypical antipsychotic agents. Synthesis, structure-activity relationship, molecular modeling, and biological studies". Journal of Medicinal Chemistry 45 (2): 344–59. January 2002. doi:10.1021/jm010982y. PMID 11784139. 
  8. ↑ 8.0 8.1 8.2 "Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist". The Journal of Pharmacology and Experimental Therapeutics 315 (3): 1278–87. December 2005. doi:10.1124/jpet.105.092155. PMID 16135699. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16135699. 
  9. ↑ 9.0 9.1 "Octoclothepin enantiomers. A reinvestigation of their biochemical and pharmacological activity in relation to a new receptor-interaction model for dopamine D-2 receptor antagonists". Journal of Medicinal Chemistry 34 (7): 2023–30. July 1991. doi:10.1021/jm00111a015. PMID 1676758. 
  10. ↑ 10.0 10.1 "Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors". The Journal of Pharmacology and Experimental Therapeutics 268 (3): 1403–10. March 1994. PMID 7908055. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7908055. 
  11. ↑ 11.0 11.1 11.2 "Exploring the neuroleptic substituent in octoclothepin: potential ligands for positron emission tomography with subnanomolar affinity for α(1)-adrenoceptors". Journal of Medicinal Chemistry 53 (19): 7021–34. October 2010. doi:10.1021/jm100652h. PMID 20857909. 
  12. ↑ "Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist". The Journal of Pharmacology and Experimental Therapeutics 314 (3): 1310–21. September 2005. doi:10.1124/jpet.105.087965. PMID 15947036. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15947036. 
  13. ↑ "Conformational analysis and structural comparisons of (1R,3S)-(+)- and (1S,3R)-(−)-tefludazine, (S)-(+)- and (R)-(−)-octoclothepin, and (+)-dexclamol in relation to dopamine receptor antagonism and amine-uptake inhibition". Journal of Medicinal Chemistry 31 (2): 306–12. February 1988. doi:10.1021/jm00397a006. PMID 2892932. 
  14. ↑ Textbook of drug design and discovery. CRC Press. 25 July 2002. p. 108. ISBN 978-0-415-28288-8. https://books.google.com/books?id=EL-UI6t8omQC&pg=PA108. Retrieved 26 November 2011. 



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