Clorotepine

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
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
IUPAC name
  • 1-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-methylpiperazine
CAS Number
  • 13448-22-1
    4789-68-8 (maleate)
    42505-79-3 (mesylate)
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H21ClN2S
Molar mass344.90 g·mol−1
3D model (JSmol)
SMILES
  • Clc4cc2c(Sc1ccccc1CC2N3CCN(C)CC3)cc4
InChI
  • InChI=1S/C19H21ClN2S/c1-21-8-10-22(11-9-21)17-12-14-4-2-3-5-18(14)23-19-7-6-15(20)13-16(17)19/h2-7,13,17H,8-12H2,1H3
  • Key:XRYLGRGAWQSVQW-UHFFFAOYSA-N

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. p. 265. ISBN 978-3-88763-075-1. Retrieved 26 November 2011.
  2. Ganellin CR, Triggle DJ, Macdonald F (1997). Dictionary of pharmacological agents. CRC Press. p. 500. ISBN 978-0-412-46630-4. Retrieved 26 November 2011.
  3. Metysová J, Metys J, Dlabac A, Kazdová E, Valchár M (1980). "Pharmacological properties of a potent neuroleptic drug octoclothepin". Acta Biologica et Medica Germanica. 39 (6): 723–40. PMID 6893891.
  4. Cain CK (1 January 1971). Annual Reports in Medicinal Chemistry. Academic Press. p. 5. ISBN 978-0-12-040506-0. Retrieved 26 November 2011.
  5. Protiva M (2010). "ChemInform Abstract: Fifty Years in Chemical Drug Research". ChemInform. 23 (9): no. doi:10.1002/chin.199209338. ISSN 0931-7597.
  6. Melich H (1971). "[Clotepin]". Cas. Lek. Cesk. (in Czech). 110 (17): 404–5. PMID 5576292.
  7. Campiani G, Butini S, Gemma S, et al. (January 2002). "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. doi:10.1021/jm010982y. PMID 11784139.
  8. Burstein ES, Ma J, Wong S, et al. (December 2005). "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. doi:10.1124/jpet.105.092155. PMID 16135699. S2CID 2247093.
  9. Bøgesø KP, Liljefors T, Arnt J, Hyttel J, Pedersen H (July 1991). "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. doi:10.1021/jm00111a015. PMID 1676758.
  10. Roth BL, Craigo SC, Choudhary MS, et al. (March 1994). "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. PMID 7908055.
  11. Kristensen JL, Püschl A, Jensen M, et al. (October 2010). "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. doi:10.1021/jm100652h. PMID 20857909.
  12. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R (September 2005). "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. doi:10.1124/jpet.105.087965. PMID 15947036. S2CID 24248896.
  13. Liljefors T, Bøgesø KP (February 1988). "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. doi:10.1021/jm00397a006. PMID 2892932.
  14. Krogsgaard-Larsen P, Liljefors T, Madsen U (25 July 2002). Textbook of drug design and discovery. CRC Press. p. 108. ISBN 978-0-415-28288-8. Retrieved 26 November 2011.
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