SCH 23390 hydrochloride (Synonyms: R-(+)-SCH-23390 hydrochloride)

SCH 23390 hydrochloride is a highly potent and selective dopamine D1-like receptor antagonist with a K(i) of 0.2 and 0.3 nM for the D1 and D5 dopamine receptor subtypes, respectively. In vitro, it also binds with high affinity to the 5-HT2 and 5-HT1C serotonin receptor subtypes^[1].As a potent and high efficacy human 5-HT2C receptor agonist with a Ki of 9.3 nM. SCH-23390 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channels with an IC50 of 268 nM^[2,3].

SCH 23390 hydrochloride (1 μM) treatment reverses the inhibitory effects of Isosibiricin on NLRP3 expression and the cleavages of caspase-1 and IL-1β in the LPS-induced BV-2 cells. SCH 23390 hydrochloride could reverse the Isosibiricin-mediated inhibition of the NLRP3/caspase-1 inflammasome pathway^[4].Pretreatment of primary astrocytes with the DRD1 antagonistSCH 23390 hydrochloride did not reduce cabergoline induced GSH synthesis^[6].

In spontaneously hypertensive rats, fenoldopam produced a dose-dependent reduction in arterial pressure and a significant increase in mesenteric and renal blood flow, and pretreatment with the DA 1-like receptor antagonist SCH 23390 hydrochloride significantly attenuated these effects^[5]. C57BL/6J mice were injected with the D1R antagonist SCH 23390 hydrochloride, and a decrease in social behavior was seen, producing autism-like behavior^[7]. The effects of Aβ on memory in Per2 mice were investigated, and the increased Aβ levels did not influence the memory performance of Per2 mice after SCH 23390 hydrochloride treatment^[9].SCH 23390 hydrochloride and Haloperidolwere administered during CPP. The accompanying changes in phosphorylation of extracellular signal-regulated kinase (ERK) in MLDS related brain regions, including the ventral tegmental area (VTA), caudate putamen (CPu), prefrontal cortex (PFC), and nucleus accumbens (NAc) were measured in the CPP mice. Results revealed that 60% N2O induced CPP in the gas-administered mice and promoted the ERK phosphorylation (p-ERK) in the NAc and CPu during the test session of the CPP test. Pretreatment of SCH 23390 hydrochloride(0.5 mg/kg) inhibited the acquisition of N2O-induced CPP and the enhanced p-ERK in NAc^[8].

References:
[1]: Bourne JA. SCH 23390: the first selective dopamine D1-like receptor antagonist. CNS Drug Rev. 2001 Winter;7(4):399-414. doi: 10.1111/j.1527-3458.2001.tb00207.x. PMID: 11830757; PMCID: PMC6741643.
[2]: Millan MJ, Newman-Tancredi A, et,al. The "selective" dopamine D1 receptor antagonist, SCH23390, is a potent and high efficacy agonist at cloned human serotonin2C receptors. Psychopharmacology (Berl). 2001 Jun;156(1):58-62. doi: 10.1007/s002130100742. PMID: 11465634.
[3]: Kuzhikandathil EV, Oxford GS. Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly inhibits G protein-coupled inwardly rectifying potassium channels. Mol Pharmacol. 2002 Jul;62(1):119-26. doi: 10.1124/mol.62.1.119. PMID: 12065762.
[4]: Wang YH, Lv HN, et,al. Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway. Acta Pharmacol Sin. 2020 Feb;41(2):173-180. doi: 10.1038/s41401-019-0296-7. Epub 2019 Sep 10. PMID: 31506572; PMCID: PMC7471458.
[5]: Crockett SL, Harris M, et,al. Role of dopamine and selective dopamine receptor agonists on mouse ductus arteriosus tone and responsiveness. Pediatr Res. 2020 May;87(6):991-997. doi: 10.1038/s41390-019-0716-x. Epub 2019 Dec 9. PMID: 31816622; PMCID: PMC7196482.
[6]: Wei Y, Lu M, et,al. Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nat Commun. 2020 Feb 18;11(1):941. doi: 10.1038/s41467-020-14788-x. PMID: 32071304; PMCID: PMC7029000.
[7]: Li Y, Luo ZY, et,al. The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice. Microbiome. 2020 Aug 20;8(1):120. doi: 10.1186/s40168-020-00884-z. PMID: 32819434; PMCID: PMC7441571.
[8]: Yang T, Yue G, et,al. SCH 23390 inhibits the acquisition of nitrous oxide-induced conditioned place preference and the changes in ERK phosphorylation expression in nucleus accumbens of mice. Neurosci Lett. 2022 Jun 11;781:136674. doi: 10.1016/j.neulet.2022.136674. Epub 2022 May 4. PMID: 35525502.
[9]: Kim M, Custodio RJ, et,al. Per2 Expression Regulates the Spatial Working Memory of Mice through DRD1-PKA-CREB Signaling. Mol Neurobiol. 2022 Jul;59(7):4292-4303. doi: 10.1007/s12035-022-02845-z. Epub 2022 May 4. PMID: 35508866.