Piquindone

Piquindone

Piquindone
Systematic (IUPAC) name
(4aS,8aS)-3-ethyl-2,6-dimethyl-1,4a,5,6,7,8,8a,9-octahydro-4H-pyrrolo[2,3-g]isoquinolin-4-one
Clinical data
Legal status
  • Uncontrolled
Routes Oral
Identifiers
CAS number
83784-19-4 (hydrochloride)
ATC code None
PubChem
ChemSpider
UNII  YesY
ChEMBL
Chemical data
Formula C15H22N2O 
Mol. mass 246.35 g/mol

Piquindone (Ro 22-1319) is an atypical antipsychotic with a tricyclic structure that was developed in the 1980s but was never marketed.[1][2][3] It acts as a selective D2 receptor antagonist,[4][5][6] though based on its effects profile its selectivity may be considered controversial. Unlike most other D2 receptor ligands, piquindone displays Na2+-dependent binding, a property it shares with tropapride, zetidoline, and metoclopramide.[7]

In clinical trials piquindone was found to possess moderate efficacy in treating positive symptoms of schizophrenia, and notably, was also modestly effective for negative symptoms, though this was just under statistical significance.[1] Additionally, relative to haloperidol, it was found to possesses significantly fewer extrapyramidal symptoms and had a much lower propensity for inducing tardive dyskinesia, indicating its atypical nature.[1][3] In addition to psychosis, piquindone has also been found to be effective in the treatment of Tourette's syndrome in numerous clinical studies.[8][9][10][11]

Synthesis

Piquindone synthesis:[12]

See also

References

  1. ^ a b c Cohen JD, Van Putten T, Marder S, Berger PA, Stahl SM (October 1987). "The efficacy of piquindone, a new atypical neuroleptic, in the treatment of the positive and negative symptoms of schizophrenia". Journal of Clinical Psychopharmacology 7 (5): 324–9.  
  2. ^ Olson GL, Cheung HC, Morgan KD, et al. (September 1981). "A dopamine receptor model and its application in the design of a new class of rigid pyrrolo[2,3-g]isoquinoline antipsychotics". Journal of Medicinal Chemistry 24 (9): 1026–34.  
  3. ^ a b Davidson AB, Boff E, MacNeil DA, Wenger J, Cook L (1983). "Pharmacological effects of Ro 22-1319: a new antipsychotic agent". Psychopharmacology 79 (1): 32–9.  
  4. ^ Nakajima T, Iwata K (November 1984). "[3H]Ro 22-1319 (piquindone) binds to the D2 dopaminergic receptor subtype in a sodium-dependent manner". Molecular Pharmacology 26 (3): 430–8.  
  5. ^ Pugh MT, O'Boyle KM, Molloy AG, Waddington JL (1985). "Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU24213". Psychopharmacology 87 (3): 308–12.  
  6. ^ Molloy AG, O'Boyle KM, Pugh MT, Waddington JL (July 1986). "Locomotor behaviors in response to new selective D-1 and D-2 dopamine receptor agonists, and the influence of selective antagonists". Pharmacology, Biochemistry, and Behavior 25 (1): 249–53.  
  7. ^ Collin S, Vercauteren DP, Vanderveken D, Evrard G, Durant F (March 1989). "Structural requirements of Na+-dependent antidopaminergic agents: Tropapride, Piquindone, Zetidoline, and Metoclopramide. Comparison with Na+-independent ligands". Journal of Computer-aided Molecular Design 3 (1): 39–53.  
  8. ^ Uhr SB, Berger PA, Pruitt B, Stahl SM (October 1984). "Treatment of Tourette's syndrome with RO22-1319, a D-2-receptor antagonist". The New England Journal of Medicine 311 (15): 989.  
  9. ^ Uhr SB, Pruitt B, Berger PA, Stahl SM (April 1986). "Case report of four patients with Tourette syndrome treated with piquindone, a D2 receptor antagonist". Journal of Clinical Psychopharmacology 6 (2): 128–30.  
  10. ^ Uhr SB, Pruitt B, Berger PA, Stahl SM (July 1986). "Improvement of symptoms in Tourette syndrome by piquindone, a novel dopamine-2 receptor antagonist". International Clinical Psychopharmacology 1 (3): 216–20.  
  11. ^ Jiménez-Jiménez FJ, García-Ruiz PJ (2001). "Pharmacological options for the treatment of Tourette's disorder". Drugs 61 (15): 2207–20.  
  12. ^ Coffen, D. L.; Hengartner, U.; Katonak, D. A.; Mulligan, M. E.; Burdick, D. C.; Olson, G. L.; Todaro, L. J. (1984). "Syntheses of an antipsychotic pyrrolo[2,3-g]isoquinoline from areca alkaloids". The Journal of Organic Chemistry 49 (26): 5109.