Sonepiprazole

Sonepiprazole (U-101,387, PNU-101,387-G) is a drug of the phenylpiperazine class which acts as a highly selective D4 receptor antagonist.[1] In animals, unlike D2 receptor antagonists like haloperidol, sonepiprazole does not block the behavioral effects of amphetamine or apomorphine, does not alter spontaneous locomotor activity on its own, and lacks extrapyramidal and neuroendocrine effects.[2] However, it does reverse the prepulse inhibition deficits induced by apomorphine,[3] and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment.[4][5] As a result, it was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.[6][7]

Sonepiprazole
Clinical data
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
IUPAC name
  • 4-(4-{2-[(1S)-3,4-dihydro-1H-isochromen-1-yl]ethyl}piperazin-1-yl)benzenesulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
FormulaC21H27N3O3S
Molar mass401.53 g·mol−1
3D model (JSmol)
SMILES
  • O=S(=O)(N)c1ccc(cc1)N2CCN(CC2)CC[C@@H]4OCCc3ccccc34

See also

References

  1. TenBrink RE, Bergh CL, Duncan JN, et al. (June 1996). "(S)-(−)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist". Journal of Medicinal Chemistry. 39 (13): 2435–7. doi:10.1021/jm960084f. PMID 8691438.
  2. Merchant KM, Gill GS, Harris DW, et al. (December 1996). "Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist". The Journal of Pharmacology and Experimental Therapeutics. 279 (3): 1392–403. PMID 8968364.
  3. Mansbach RS, Brooks EW, Sanner MA, Zorn SH (January 1998). "Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition". Psychopharmacology. 135 (2): 194–200. doi:10.1007/s002130050501. PMID 9497025. S2CID 9246828.
  4. Rubinstein M, Cepeda C, Hurst RS, et al. (June 2001). "Dopamine D4 receptor-deficient mice display cortical hyperexcitability". Journal of Neuroscience. 21 (11): 3756–63. doi:10.1523/JNEUROSCI.21-11-03756.2001. hdl:11336/79333. PMC 6762699. PMID 11356863.
  5. Arnsten AF, Murphy B, Merchant K (October 2000). "The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys". Neuropsychopharmacology. 23 (4): 405–10. doi:10.1016/S0893-133X(00)00133-0. PMID 10989267.
  6. Unangst PC, Capiris T, Connor DT, et al. (August 1997). "Chromeno[3,4-c]pyridin-5-ones: selective human dopamine D4 receptor antagonists as potential antipsychotic agents". Journal of Medicinal Chemistry. 40 (17): 2688–93. doi:10.1021/jm970170v. PMID 9276014.
  7. Corrigan MH, Gallen CC, Bonura ML, Merchant KM (March 2004). "Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial". Biological Psychiatry. 55 (5): 445–51. doi:10.1016/j.biopsych.2003.10.004. PMID 15023570. S2CID 108634.
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