Chemistry:Sonepiprazole
Sonepiprazole (INN; developmental code names U-101387 and PNU-101387) is a highly selective dopamine D4 receptor antagonist of the phenylpiperazine family.[1][2]
The drug showed high affinity for the dopamine D4.2 receptor (Ki = 24 nM) and negligible affinity for other dopamine receptors (Ki = >1,000 nM).[3] 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.[4][3] However, it does reverse the prepulse inhibition deficits induced by apomorphine,[5] and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment.[6][7]
Sonepiprazole was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to olanzapine, no benefits were found, and it was not researched further for this use.[8][9] It was under development by Pharmacia Corporation for the treatment of schizophrenia, and reached phase 2 clinical trials for this indication, but development was discontinued in March 2001.[1]
See also
- List of investigational antipsychotics
- Substituted phenylpiperazine
- Lu 35-138
- PNU-142633
- Terikalant
References
- ↑ 1.0 1.1 "Sonepiprazole". 30 March 2001. https://adisinsight.springer.com/drugs/800007223.
- ↑ "(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. June 1996. doi:10.1021/jm960084f. PMID 8691438.
- ↑ 3.0 3.1 "Lu 35-138 ((+)-(S)-3-{1-[2-(1-acetyl-2,3-dihydro-1H-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl}-6-chloro-1H-indole), a dopamine D4 receptor antagonist and serotonin reuptake inhibitor: characterisation of its in vitro profile and pre-clinical antipsychotic potential". Eur J Pharmacol 573 (1-3): 148–160. November 2007. doi:10.1016/j.ejphar.2007.06.052. PMID 17689529.
- ↑ "Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist". The Journal of Pharmacology and Experimental Therapeutics 279 (3): 1392–403. December 1996. doi:10.1016/S0022-3565(25)21300-3. PMID 8968364. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8968364.
- ↑ "Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition". Psychopharmacology 135 (2): 194–200. January 1998. doi:10.1007/s002130050501. PMID 9497025. http://link.springer.de/link/service/journals/00213/bibs/8135002/81350194.htm.
- ↑ "Dopamine D4 receptor-deficient mice display cortical hyperexcitability". Journal of Neuroscience 21 (11): 3756–63. June 2001. doi:10.1523/JNEUROSCI.21-11-03756.2001. PMID 11356863.
- ↑ "The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys". Neuropsychopharmacology 23 (4): 405–10. October 2000. doi:10.1016/S0893-133X(00)00133-0. PMID 10989267.
- ↑ "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. August 1997. doi:10.1021/jm970170v. PMID 9276014.
- ↑ "Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial". Biological Psychiatry 55 (5): 445–51. March 2004. doi:10.1016/j.biopsych.2003.10.004. PMID 15023570.
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