ADROGOLIDE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H25NO4S.ClH
Molecular Weight	435.964
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]12CCC3=CC(OC(C)=O)=C(OC(C)=O)C=C3[C@@]1([H])C4=C(CN2)SC(CCC)=C4

InChI

InChIKey=NPEZSCRKHFTLPE-MYXGOWFTSA-N

InChI=1S/C22H25NO4S.ClH/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;1H/t18-,22+;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607045
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D1 receptor 101 Target ID: CHEMBL2056 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607045	Agonist 2678	51.0 nM [Ki]
Dopamine D5 receptor 12 Target ID: CHEMBL1850 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607045	Agonist 2678	15.0 nM [Ki]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607045	Agonist 2678	750.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11176963 https://www.pharmacodia.com/yaodu/html/v1/chemicals/ee228bd5b36762c84cd0641eb267440b.html	Primary		Phase II 1132	Unknown Approved Use Unknown
Cocaine addiction 28 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11607045	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
15.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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

Value	Dose	Analyte	Population
10.6 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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

T_1/2

Value	Dose	Analyte	Population
3.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10564839/	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

Dose	Population	Adverse events
20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	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: https://pubmed.ncbi.nlm.nih.gov/11607045
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: https://pubmed.ncbi.nlm.nih.gov/10360765	unhealthy n = 14 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10360765	Other AEs: headache, Flushing... Other AEs: headache Flushing Nausea Injection site reaction Sources: https://pubmed.ncbi.nlm.nih.gov/10360765

AEs

AE	Significance	Dose	Population
Dizziness	31%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
Postural hypotension	31%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
vasodilatation	31%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
vomiting	31%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
Nausea	38%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
Asthenia	62%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
headache	62%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
injection site reaction	85%	20 mg single, intravenous (max) Studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
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: https://pubmed.ncbi.nlm.nih.gov/11607045	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: Parkinson disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/11607045
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: https://pubmed.ncbi.nlm.nih.gov/10360765	unhealthy n = 14 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10360765
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: https://pubmed.ncbi.nlm.nih.gov/10360765	unhealthy n = 14 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10360765
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: https://pubmed.ncbi.nlm.nih.gov/10360765	unhealthy n = 14 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10360765
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: https://pubmed.ncbi.nlm.nih.gov/10360765	unhealthy n = 14 Health Status: unhealthy Condition: Parkinson disease Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/10360765

Sourcing

Vendor/Aggregator	ID	URL
Compound Cloud	176876
Compound Cloud	6918298
MuseChem	I001236	https://www.musechem.com/product/I001236.html
MuseChem	M127354	https://www.musechem.com/product/M127354.html

PubMed

Title	Date	PubMed
(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	7658429
Hyperactivity and behavioral seizures in rodents following treatment with the dopamine D1 receptor agonists A-86929 and ABT-431.	1996 Dec 19	8997599
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	8558425
ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease.	1999 Jun	10360765
Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans.	1999 Mar	10227086

Patents

Sample Use Guides

In Vivo Use Guide

2, 4 mg over a 1-h period immediately prior to cocaine self-administration sessions

Route of Administration: Intravenous

In Vitro Use Guide

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.

Name

Type

Language

ADROGOLIDE HYDROCHLORIDE

Official Name

English

ADROGOLIDE HCL

Common Name

English

BENZO(F)THIENO(2,3-C)QUINOLINE-9,10-DIOL, 4,5,5A,6,7,11B-HEXAHYDRO-2-PROPYL-, DIACETATE (ESTER), HYDROCHLORIDE, (5AR-TRANS)-

Common Name

English

ADROGOLIDE HYDROCHLORIDE [USAN]

Common Name

English

(5aR,11bS)-4,5,5a,6,7,11b-Hexahydro-2-propylbenzo[f]thieno[2,3-c]quinoline-9,10-diol diacetate (ester), hydrochloride

Common Name

English

A-93431.1

Code

English

ABT-431

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C66884