Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C17H18ClNO.C4H4O4 |
| Molecular Weight | 403.856 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.CN1CCC2=CC(Cl)=C(O)C=C2[C@H](C1)C3=CC=CC=C3
InChI
InChIKey=FGHVSEXHEAUJBT-HFNHQGOYSA-N
InChI=1S/C17H18ClNO.C4H4O4/c1-19-8-7-13-9-16(18)17(20)10-14(13)15(11-19)12-5-3-2-4-6-12;5-3(6)1-2-4(7)8/h2-6,9-10,15,20H,7-8,11H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t15-;/m1./s1
SCH-23390 is a potent and selective antagonist of the dopamine-1 and dopamine-5 receptors (Ki = 0.2 and 0.3 nM respectively). It was found to prevent death from d-amphetamine overdose in rats and has also been investigated as a potential treatment for Parkinson's Disease and Bipolar Disorder. A single clinical trial was conducted in healthy humans where SCH-23390 induced akathisia (motor restlessness). Preclinical and clinical trials as therapeutic have been discontinued due to side-effects and lack of efficacy. However, it should be noted that a C11 radiolabeled version of the compound has been synthesized and used as a PET imaging probe for the study of Parkinson's Disease and Huntington's Disease.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P21728 Gene ID: 1812.0 Gene Symbol: DRD1 Target Organism: Homo sapiens (Human) |
0.2 nM [Ki] | ||
Target ID: P21918 Gene ID: 1816.0 Gene Symbol: DRD5 Target Organism: Homo sapiens (Human) |
0.3 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats. | 1991 |
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| Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice. | 1991 |
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| D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. | 1992 |
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| D1 dopamine receptor activation of multiple transcription factor genes in rat striatum. | 1992 Apr |
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| Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D1 agonist C-APB in mice. | 1999 Aug |
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| Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice. | 1999 Jul 14 |
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| Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs. | 1999 Mar |
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| D1 receptor blockade improves L-dopa-induced dyskinesia but worsens parkinsonism in MPTP monkeys. | 1999 Mar 10 |
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| Effects of SCH 23390, raclopride, and haloperidol on morphine withdrawal-induced aggression in male mice. | 1999 Sep |
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| Halogenated boldine derivatives with enhanced monoamine receptor selectivity. | 2000 Apr |
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| Effect of dopamine agonists and antagonists on the lorazepam withdrawal syndrome in rats. | 2000 Mar |
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| Spatiotemporal analysis of Fos expression associated with cocaine- and PTZ-induced seizures in prenatally cocaine-treated rats. | 2001 Jul |
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| Differential effects of D1- and D2-like compounds on cocaine self-administration in Lewis and Fischer 344 inbred rats. | 2001 Nov |
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| Involvement of serotonergic and dopaminergic mechanisms in hyperthermia induced by a serotonin-releasing drug, p-chloroamphetamine in mice. | 2001 Nov 2 |
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| Hypothalamic CRH mRNA levels are differentially modulated by repeated 'binge' cocaine with or without D(1) dopamine receptor blockade. | 2001 Oct 19 |
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| Characterization of the distribution of the cocaine priming threshold and the effect of SCH23390. | 2002 Aug 16 |
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| 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. | 2002 Jul |
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| Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. | 2002 Sep 15 |
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| Combined intrastriatal dopamine D1 and serotonin 5-HT2 receptor stimulation reveals a mechanism for hyperlocomotion in 6-hydroxydopamine-lesioned rats. | 2003 |
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| Pharmacologic identification of putative D1 dopamine receptors in feline kidneys. | 2003 Aug |
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| A 68930 and dihydrexidine inhibit locomotor activity and d-amphetamine-induced hyperactivity in rats: a role of inhibitory dopamine D(1/5) receptors in the prefrontal cortex? | 2004 |
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| Effects of dopamine- and serotonin-related compounds on methamphetamine-induced self-injurious behavior in mice. | 2004 Dec |
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| Effects of dopamine D1 receptor full agonists in rats trained to discriminate SKF 38393. | 2004 Feb |
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| The transcription factor NGFI-B (Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal neuropeptide gene expression. | 2004 Feb |
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| Dopamine receptor activation in bovine pinealocyte via a cAMP-dependent transcription pathway. | 2005 Apr |
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| Dopamine D1 and D2 receptor contributions to L-DOPA-induced dyskinesia in the dopamine-depleted rat. | 2005 Aug |
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| Validation of the l-dopa-induced dyskinesia in the 6-OHDA model and evaluation of the effects of selective dopamine receptor agonists and antagonists. | 2005 Dec 15 |
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| The role of tissue plasminogen activator in methamphetamine-related reward and sensitization. | 2005 Feb |
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| Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. | 2005 Jan 18 |
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| Dopamine uptake inhibitor-induced rotation in 6-hydroxydopamine-lesioned rats involves both D1 and D2 receptors but is modulated through 5-hydroxytryptamine and noradrenaline receptors. | 2005 Mar |
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| Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists. | 2005 Oct |
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| Histamine H3 receptor agonist- and antagonist-evoked vacuous chewing movements in 6-OHDA-lesioned rats occurs in an absence of change in microdialysate dopamine levels. | 2006 Dec 15 |
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| The influence of central administration of dopaminergic and cholinergic agents on morphine-induced amnesia in morphine-sensitized mice. | 2006 Jan |
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| Influence of nitric oxide on morphine-induced amnesia and interactions with dopaminergic receptor agents. | 2006 Jun 15 |
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| Inhibition of methylphenidate-induced gene expression in the striatum by local blockade of D1 dopamine receptors: interhemispheric effects. | 2006 Jun 30 |
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| Delayed L-DOPA-induced hyperalgesia. | 2006 Nov |
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| Pharmacological studies of the opioids, mood stabilizer and dopaminergic drugs on pilocarpine-induced seizures and status epilepticus. | 2006 Nov 13 |
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| Cocaine increases endoplasmic reticulum stress protein expression in striatal neurons. | 2007 Mar 16 |
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| Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors. | 2007 Oct 1 |
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| Effects of dopamine and NMDA receptors on cocaine-induced Fos expression in the striatum of Fischer rats. | 2008 Dec 3 |
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| Dopamine neurotransmission is involved in the attenuating effects of 5-HT3 receptor antagonist MDL 72222 on acute methamphetamine-induced locomotor hyperactivity in mice. | 2008 Jan |
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| Role of dopamine D1-like receptors in methamphetamine locomotor responses of D2 receptor knockout mice. | 2008 Jul |
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| Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine. | 2008 Mar 1 |
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| Transient D1 dopamine receptor expression on prefrontal cortex projection neurons: relationship to enhanced motivational salience of drug cues in adolescence. | 2008 Mar 5 |
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| Effect of cocaine on Fas-associated protein with death domain in the rat brain: individual differences in a model of differential vulnerability to drug abuse. | 2009 Apr |
Sample Use Guides
SCH-23390 was tested in four healthy subjects at doses of 310–810 micrograms delivered intravenously. SCH-23390 induced akathisia at the three highest doses.
Route of Administration:
Intravenous
Rat brain striatal slices were preincubated with [3H]GABA and superfused in the presence of the GABA transport inhibitor nipecotic and GABA aminotransferase inhibitor aminooxyacetic acids. GABA efflux was estimated by monitoring the efflux of [3H]GABA. The overflow of GABA evoked by electrical field stimulation was blocked by 0.5 - 10 microM of SCH 23390.
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3T51J24N1F
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87134-87-0
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6440792
Created by
admin on Fri Dec 15 16:46:10 GMT 2023 , Edited by admin on Fri Dec 15 16:46:10 GMT 2023
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ACTIVE MOIETY
SUBSTANCE RECORD
