Background:

SCH 23390 hydrochloride is a potent dopamine receptor D1 antagonist with Ki values of 0.2 and 0.3 nM for the D1 and D5.

The commercially available hydrochloride salt has a molecular weight of 324.25 and is a white solid soluble in water (8 mg/mL), DMSO (3 mg/mL), or ethanol (2 mg/mL)[1]. SCH 23390 also shows high affinity (Ki=9.3 nM) at h5-HT2C sites[2]. SCH23390 blocks endogenous GIRK currents induced by either somatostatin or D3 dopamine receptors in AtT-20 cells (IC50=268 nM)[3].

SCH 23390 has been a major tool in gaining a better understanding of the role of the dopamine system. SCH 23390 is a very short-acting compound with an elimination half-life of around 25 min following administration of 0.3 mg/kg i.p. in the rat[1]. The repeated administration of SCH 23390 (0.05 mg/kg s.c., thrice daily for 21 days) enhances the steady-state density of dopamine D1 receptors in the striatum (+30%) and substantia nigra (+24%). This treatment also increases the production rates of dopamine D1 receptors in the striatum (+44%) and substantia nigra (+54%)[4]. Systemic SCH 23390 reduces saccharin seeking evidenced by a significant reduction in active lever responding and a significant reduction in the number of active lever-contingent deliveries of the tone + light cue following pretreatment with 10 μg/kg SCH 23390[5].

参考文献:
[1]. Bourne JA, et al . SCH 23390: the first selective dopamine D1-like receptor antagonist. CNS Drug Rev. 2001 Winter;7(4):399-414.
[2]. Millan MJ, 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.
[3]. Kuzhikandathil EV, et al. 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-coupledinwardly rectifying potassium channels. Mol Pharmacol. 2002 Jul;62(1):119-26.
[4]. Giorgi O, et al. Chronic treatment with SCH 23390 increases the production rate of dopamine D1 receptors in the nigro-striatal system of the rat. Eur J Pharmacol. 1993 Apr 15;245(2):139-45.
[5]. Aoyama K, et al. Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats. Appetite. 2016 Oct 1;105:8-13.