U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H25NO4S
Molecular Weight 399.5051
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ADROGOLIDE

SMILES

CCCc1cc2c(CN[C@]3([H])CCc4cc(c(cc4[C@@]23[H])OC(=O)C)OC(=O)C)s1

InChI

InChIKey=KTEBZVJGMARTOQ-GCJKJVERSA-N
InChI=1S/C22H25NO4S/c1-4-5-15-9-17-21(28-15)11-23-18-7-6-14-8-19(26-12(2)24)20(27-13(3)25)10-16(14)22(17)18/h8-10,18,22-23H,4-7,11H2,1-3H3/t18-,22+/m1/s1

HIDE SMILES / InChI

Molecular Formula C22H25NO4S
Molecular Weight 399.5051
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800006590 | https://www.ncbi.nlm.nih.gov/pubmed/8558425 | https://www.ncbi.nlm.nih.gov/pubmed/10360765

Adrogolide is a chemically stable prodrug of the dopamine D1 receptor agonist A-86929. Adrogolide is rapidly converted in plasma to A-86929. A-86929 has high affinity and functional selectivity for the dopamine D1 receptor. Adrogolide has been in phase II clinical trials for the treatment of Parkinson's disease and cocaine abuse. However, this research has been discontinued. The adverse events associated with its use of adrogolide were of mild-to-moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
51.0 nM [Ki]
15.0 nM [Ki]
750.0 nM [Ki]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.2 ng/mL
3.3 mg 1 times / day single, respiratory
dose: 3.3 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
19.1 ng/mL
6.6 mg single, respiratory
dose: 6.6 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
13.6 ng/mL
19.8 mg single, respiratory
dose: 19.8 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
24.2 ng/mL
13.2 mg single, respiratory
dose: 13.2 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
19.4 ng/mL
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10.6 ng × h/L
3.3 mg 1 times / day single, respiratory
dose: 3.3 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
16.1 ng × h/mL
6.6 mg single, respiratory
dose: 6.6 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
22.5 ng × h/mL
19.8 mg single, respiratory
dose: 19.8 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
26 ng × h/mL
13.2 mg single, respiratory
dose: 13.2 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
42.7 ng × h/mL
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.2 h
3.3 mg 1 times / day single, respiratory
dose: 3.3 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.2 h
6.6 mg single, respiratory
dose: 6.6 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5.5 h
19.8 mg single, respiratory
dose: 19.8 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.2 h
13.2 mg single, respiratory
dose: 13.2 mg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.3 h
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
A-86929 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Disc. AE: Nausea and vomiting...
Other AEs: Asthenia, Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea and vomiting (severe, 1 pt)
Other AEs:
Asthenia (62%)
Nausea (38%)
headache (62%)
vomiting (31%)
Postural hypotension (31%)
injection site reaction (85%)
vasodilatation (31%)
Dizziness (31%)
Sources:
40 mg 1 times / day multiple, intravenous (unknown)
Highest studied dose
Dose: 40 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 14
Health Status: unhealthy
Condition: Parkinson disease
Sex: M+F
Food Status: UNKNOWN
Population Size: 14
Sources:
Other AEs: headache, Flushing...
Other AEs:
headache
Flushing
Nausea
Injection site reaction
Sources:
AEs

AEs

AESignificanceDosePopulation
Dizziness 31%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Postural hypotension 31%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
vasodilatation 31%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
vomiting 31%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Nausea 38%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Asthenia 62%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
headache 62%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
injection site reaction 85%
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Nausea and vomiting severe, 1 pt
Disc. AE
20 mg single, intravenous (max)
Studied dose
Dose: 20 mg
Route: intravenous
Route: single
Dose: 20 mg
Sources:
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: Parkinson disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources:
Flushing
40 mg 1 times / day multiple, intravenous (unknown)
Highest studied dose
Dose: 40 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 14
Health Status: unhealthy
Condition: Parkinson disease
Sex: M+F
Food Status: UNKNOWN
Population Size: 14
Sources:
Injection site reaction
40 mg 1 times / day multiple, intravenous (unknown)
Highest studied dose
Dose: 40 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 14
Health Status: unhealthy
Condition: Parkinson disease
Sex: M+F
Food Status: UNKNOWN
Population Size: 14
Sources:
Nausea
40 mg 1 times / day multiple, intravenous (unknown)
Highest studied dose
Dose: 40 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 14
Health Status: unhealthy
Condition: Parkinson disease
Sex: M+F
Food Status: UNKNOWN
Population Size: 14
Sources:
headache
40 mg 1 times / day multiple, intravenous (unknown)
Highest studied dose
Dose: 40 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 14
Health Status: unhealthy
Condition: Parkinson disease
Sex: M+F
Food Status: UNKNOWN
Population Size: 14
Sources:
PubMed

PubMed

TitleDatePubMed
(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431).
1995 Sep 1
Hyperactivity and behavioral seizures in rodents following treatment with the dopamine D1 receptor agonists A-86929 and ABT-431.
1996 Dec 19
ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.
1996 Jan
ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease.
1999 Jun
Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans.
1999 Mar
Patents

Sample Use Guides

2, 4 mg over a 1-h period immediately prior to cocaine self-administration sessions
Route of Administration: Intravenous
The EC50 value of A-86929 at cloned human dopamine D1 receptors was more than 400 times greater than that observed at the cloned human dopamine D2 receptor, and the potency of A-86929 was nearly 10-fold greater at the human dopamine D5 than at the dopamine D1 receptor.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:22:48 UTC 2021
Edited
by admin
on Sat Jun 26 09:22:48 UTC 2021
Record UNII
YC3281G42A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ADROGOLIDE
INN  
INN  
Official Name English
BENZO(F)THIENO(2,3-C)QUINOLINE-9,10-DIOL, 4,5,5A,6,7,11B-HEXAHYDRO-2-PROPYL-, DIACETATE (ESTER), (5AR-TRANS)-
Common Name English
ADROGOLIDE [INN]
Common Name English
(5AR,11BS)-4,5,5A,6,7,11B-HEXAHYDRO-2-PROPYLBENZO(F)THIENOL(2,3-C)QUINOLINE-9,10-DIOL DIACETATE (ESTER)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C66884
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C73308
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
INN
7915
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
CAS
171752-56-0
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
EPA CompTox
171752-56-0
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL2104655
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
PUBCHEM
176876
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
FDA UNII
YC3281G42A
Created by admin on Sat Jun 26 09:22:49 UTC 2021 , Edited by admin on Sat Jun 26 09:22:49 UTC 2021
PRIMARY
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SALT/SOLVATE -> PARENT
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