ROXINDOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H26N2O
Molecular Weight	346.4653
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC2=C(NC=C2CCCCN3CCC(=CC3)C4=CC=CC=C4)C=C1

InChI

InChIKey=HGEYJZMMUGWEOT-UHFFFAOYSA-N

InChI=1S/C23H26N2O/c26-21-9-10-23-22(16-21)20(17-24-23)8-4-5-13-25-14-11-19(12-15-25)18-6-2-1-3-7-18/h1-3,6-7,9-11,16-17,24,26H,4-5,8,12-15H2

HIDE SMILES / InChI

Molecular Formula	C23H26N2O
Molecular Weight	346.4653
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8775758

Roxindole (EMD-49,980) is a dopaminergic and serotonergic drug which was originally developed for the treatment of schizophrenia. Roxindole has also been investigated as a therapy for the major depressive disorder, Parkinson's disease, and prolactinoma. Roxindole is dopamine autoreceptor-selective agonistic drug with high affinity to D2-like receptors and with much lower affinities to D1-like, % and ol2, muscarinic and 5HT 2 receptors. Additionally, Roxindole exerts 5HT uptake inhibition and 5HT1A agonistic effects. The bioavailability of Roxindole has been estimated at 5% due to a high first-pass metabolization. On the other hand, in 14C distribution studies, Roxindole has crossed the blood-brain barrier readily and the brain concentrations at all intervals have been much higher than corresponding plasma levels. In clinical trials, Roxindole ‘s antipsychotic efficacy was only modest but it was unexpectedly found to produce potent and rapid antidepressant and anxiolytic effects. However, the clinical development of Roxindole was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 1a (5-HT1a) receptor 177 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20022748	Agonist 2752	0.8 nM [IC50]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8759640	Agonist 2752	0.37 nM [EC50]
Dopamine D3 receptor 97 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8759640	Agonist 2752	0.4 nM [Ki]
Dopamine D4 receptor 76 Target ID: CHEMBL219 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8759640	Agonist 2752	24.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Positive and negative symptoms of schizophrenia 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7916543	Primary	Phase IV 63	Unknown Approved Use Unknown
Parkinson's disease 232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8097280	Primary	Not Provided 511	Unknown Approved Use Unknown
Major depressive disorder 179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7870927	Primary	Not Provided 511	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
15 mg 1 times / day multiple, oral Highest studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7870927/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870927/	Sources: https://pubmed.ncbi.nlm.nih.gov/7870927/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153 CYP19A1 429	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTM2NyJ9fQ==	inconclusive [IC50 12.5893 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTM2NyJ9fQ==	inconclusive [IC50 19.9526 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/219050#section=BioAssay-Results Page: 91.0	no
CYP3A4 2633	activator 342 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDMxMzY3In19	yes [EC50 3.9811 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/219050#section=BioAssay-Results Page: 3.0	yes [IC50 0.195 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQzMTM2NyJ9fQ==	yes [IC50 31.6228 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/219050#section=BioAssay-Results Page: 126 \| 127	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/219050#section=BioAssay-Results Page: 4.0

PubMed

Title	Date	PubMed
Opioid and monoamine systems mediate the discriminative stimulus of tramadol in rats.	2004-09-13	15363988
Indolebutylamines as selective 5-HT(1A) agonists.	2004-09-09	15341483
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.	2002-11	12388668
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.	2002-11	12388667
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.	2002-11	12388666
Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells.	2001-08-08	11489662
A simple procedure for synthesis of roxindole, a dopamine D2-receptor agonist.	2001-07	11512277
Actions of roxindole at recombinant human dopamine D2, D3 and D4 and serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors.	1999-06	10431754
Roxindole, a potential antidepressant. I. Effect on the dopamine system.	1996	8811507
Treatment of Parkinson's disease with the partial dopamine agonist EMD 49980.	1993-04	8097280

Patents

Sample Use Guides

In Vivo Use Guide

Roxindole was administered at increasing daily doses from 0.3 to 30 mg for 28 days.

Route of Administration: Oral

In Vitro Use Guide

Roxindole activity was evaluated in [35S]GTPγS binding assay. Membranes of CHO cells stably expressing recombinant human 5-HT1A receptor were treated with [35S]GTPγS (0.1 nM) in assay buffer (HEPES (20 mM), pH 7.4, NaCl (100 mM), GDP (3 µM), MgCl2 (3 mM)) for 20 min at 22 °C. Efficacy is expressed as the increase in [35S]GTPγS binding observed with the agonist relative to that induced by a maximally effective concentration (10 µM) 5HT.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:33:11 GMT 2025` Edited by `admin` on `Mon Mar 31 18:33:11 GMT 2025`
Record UNII	43227SMS0O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROXINDOLE [MI]

Preferred Name

English

ROXINDOLE

Official Name

English

3-(4-(3,6-DIHYDRO-4-PHENYL-1(2H)-PYRIDYLBUTYL)INDOL-5-OL

Common Name

English

roxindole [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884