:Sonepiprazole

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = 4-(4-{2-[(1S)-3,4-dihydro-1H-isochromen-1-yl]ethyl}piperazin-1-yl)benzenesulfonamide

| image = Sonepiprazole.png

| tradename =

| pregnancy_category =

| legal_status = Uncontrolled

| routes_of_administration = Oral

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| IUPHAR_ligand = 980

| CAS_number = 170858-33-0

| ATC_prefix = none

| ATC_suffix =

| PubChem = 133079

| ChemSpiderID = 117441

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = O609V24217

| CAS_number_Ref = {{cascite|correct|CAS}}

| index2_label = as salt

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 170858-34-1

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 980MD32QLW

| C=21 | H=27 | N=3 | O=3 | S=1

| smiles = O=S(=O)(N)c1ccc(cc1)N2CCN(CC2)CC[C@@H]4OCCc3ccccc34

}}

Sonepiprazole (U-101,387, PNU-101,387-G) is a drug of the phenylpiperazine class which acts as a highly selective D₄ receptor antagonist.{{cite journal |vauthors=TenBrink RE, Bergh CL, Duncan JN, etal | title = (S)-(−)-4-[4-[2-(isochroman-1-yl)ethyl]-piperazin-1-yl] benzenesulfonamide, a selective dopamine D4 antagonist | journal = Journal of Medicinal Chemistry | volume = 39 | issue = 13 | pages = 2435–7 |date=June 1996 | pmid = 8691438 | doi = 10.1021/jm960084f }} 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.{{cite journal |vauthors=Merchant KM, Gill GS, Harris DW, etal | title = Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 279 | issue = 3 | pages = 1392–403 |date=December 1996 | doi = 10.1016/S0022-3565(25)21300-3 | pmid = 8968364 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8968364| url-access = subscription }} However, it does reverse the prepulse inhibition deficits induced by apomorphine,{{cite journal |vauthors=Mansbach RS, Brooks EW, Sanner MA, Zorn SH | title = Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition | journal = Psychopharmacology | volume = 135 | issue = 2 | pages = 194–200 |date=January 1998 | pmid = 9497025 | doi = 10.1007/s002130050501| s2cid = 9246828 | url = http://link.springer.de/link/service/journals/00213/bibs/8135002/81350194.htm| url-access = subscription }} and has also been shown to enhance cortical activity and inhibit stress-induced cognitive impairment.{{cite journal |vauthors=Rubinstein M, Cepeda C, Hurst RS, etal | title = Dopamine D4 receptor-deficient mice display cortical hyperexcitability | journal = Journal of Neuroscience | volume = 21 | issue = 11 | pages = 3756–63 |date=June 2001 | pmid = 11356863 | pmc = 6762699 | doi = 10.1523/JNEUROSCI.21-11-03756.2001| hdl = 11336/79333 }}{{cite journal |vauthors=Arnsten AF, Murphy B, Merchant K | title = The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys | journal = Neuropsychopharmacology | volume = 23 | issue = 4 | pages = 405–10 |date=October 2000 | pmid = 10989267 | doi = 10.1016/S0893-133X(00)00133-0 | doi-access = free }} 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.{{cite journal |vauthors=Unangst PC, Capiris T, Connor DT, etal | title = Chromeno[3,4-c]pyridin-5-ones: selective human dopamine D4 receptor antagonists as potential antipsychotic agents | journal = Journal of Medicinal Chemistry | volume = 40 | issue = 17 | pages = 2688–93 |date=August 1997 | pmid = 9276014 | doi = 10.1021/jm970170v }}{{cite journal |vauthors=Corrigan MH, Gallen CC, Bonura ML, Merchant KM | title = Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial | journal = Biological Psychiatry | volume = 55 | issue = 5 | pages = 445–51 |date=March 2004 | pmid = 15023570 | doi = 10.1016/j.biopsych.2003.10.004 | s2cid = 108634 }}