Systematic (IUPAC) name
Clinical data
Legal status
  • Prescription only
Routes Oral
CAS number
4789-68-8 (maleate)
42505-79-3 (mesylate)
ATC code None
Synonyms VUFB-6281; VUFB-10030
Chemical data
Formula C19H21ClN2S 
Mol. mass 344.901 g/mol

Clorotepine (INN; Clotepin, Clopiben), also known as octoclothepin or octoclothepine, is a very potent atypical neuroleptic and central depressant of the tricyclic series which was derived from perathiepin in 1965 and soon thereafter marketed in the Czech Republic by Spofa for the treatment of schizophrenic psychosis.[1][2][3][4] It is known to have high affinity for the D1,[5] D2,[6] D3,[6] D4,[6] 5-HT2A,[5] 5-HT2B,[7] 5-HT2C,[7] 5-HT6,[8] 5-HT7,[8] α1A-adrenergic,[9] α1B-adrenergic,[9] α1D-adrenergic,[9] and H1 receptors,[10] 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.[11] 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.[12]

See also


  1. ^ Index nominum 2000: international drug directory. Taylor & Francis US. 2000. p. 265.  
  2. ^ C. R Ganellin; D. J Triggle; F.. Macdonald (1997). Dictionary of pharmacological agents. CRC Press. p. 500.  
  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.  
  4. ^ Cornelius K. Cain (1 January 1971). Annual Reports in Medicinal Chemistry. Academic Press. p. 5.  
  5. ^ a b 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.  
  6. ^ a b c 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.  
  7. ^ a b 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.  
  8. ^ a b 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.  
  9. ^ a b c 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.  
  10. ^ 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.  
  11. ^ 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.  
  12. ^ Povl Krogsgaard-Larsen; Tommy Liljefors; Ulf Madsen (25 July 2002). Textbook of drug design and discovery. CRC Press. p. 108.