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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H21NO2
Molecular Weight 247.3327
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAXAGOLIDE

SMILES

[H][C@@]12CCC3=C(C=C(O)C=C3)[C@@]1([H])OCCN2CCC

InChI

InChIKey=JCSREICEMHWFAY-HUUCEWRRSA-N
InChI=1S/C15H21NO2/c1-2-7-16-8-9-18-15-13-10-12(17)5-3-11(13)4-6-14(15)16/h3,5,10,14-15,17H,2,4,6-9H2,1H3/t14-,15-/m1/s1

HIDE SMILES / InChI
Naxagolide (MK-458; L 647,339; (+)-PHNO) is a dopamine D2/D3-receptor agonist, which was studied for the treatment of patients with Parkinson's disease, but further study was discontinued. In addition, was discovered, that Naxagolide C-11 ([(11)C]-(+)-PHNO) was a potential radiotracer for imaging the high-affinity state of dopamine D2 receptors with positron emission tomography (PET) in human subjects. This radiotracer is a suitable for imaging the agonist binding sites (denoted D(2HIGH) and D(3)) of these receptors. PET studies in nonhuman primates documented that, in vivo, [(11)C]-(+)-PHNO displays a relative selectivity for D(3) compared with D(2HIGH) receptor sites and that the [(11)C]-(+)-PHNO signal is enriched in D(3) contribution compared with conventional ligands such as [(11)C] raclopride. Recently was published article reflects the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO.

Originator

Curator's Comment: # Merck & Co

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
0.24 nM [Ki]
Target ID: P35462
Gene ID: 1814.0
Gene Symbol: DRD3
Target Organism: Homo sapiens (Human)
0.6 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease.
1988 Jun
Differential effects of D1 and D2 agonists in MPTP-treated primates: functional implications for Parkinson's disease.
1990 Jun
Exploring the relationship between social attachment and dopamine D(2/3) receptor availability in the brains of healthy humans using [(11)C]-(+)-PHNO.
2017 Apr

Sample Use Guides

(up to 60 mg per day
Route of Administration: Oral
In vitro binding characteristics of the dopamine D₃/D₂ antagonist [³H]raclopride were compared to the D₃/D₂ agonist [³H](+)-PHNO (Naxagolide) in membrane preparations from rat striatum, cerebellum Lobules 9 and 10 (CB L9,10), and other cerebellar regions. In striatum, both radioligands labeled a single binding site. [³H](+)-PHNO showed higher affinity, though lower B(max) , compared with [³H]raclopride and was sensitive to inhibition by Gpp(NH)p. [³H](+)-PHNO showed significant specific binding to CB L9,10 membranes with higher affinity compared to striatal membranes. [³H](+)-PHNO binds to a high- and a low-affinity binding site in CB L9,10 membranes; the high-affinity site was not Gpp(NH)p-sensitive. [³H](+)-PHNO did not significantly bind cerebellum left hemisphere membranes.
Name Type Language
NAXAGOLIDE
INN  
INN  
Official Name English
naxagolide [INN]
Common Name English
2H-NAPHTH(1,2-B)-1,4-OXAZIN-9-OL, 3,4,4A,5,6,10B-HEXAHYDRO-4-PROPYL-, (4AR-TRANS)-
Common Name English
(R,R)-PHNO
Common Name English
(+)-PHNO
Common Name English
(+)-4-PROPYL-9-HYDROXYNAPHTHOXAZINE
Common Name English
DOPAZINOL
Common Name English
(+)-(4AR,10BR)-3,4,4A,5,6,10B-HEXAHYDRO-4-PROPYL-2H-NAPHTH(1,2-B)-1,4-OXAZIN-9-OL
Common Name English
NAZAGOLIDE
Common Name English
Code System Code Type Description
NCI_THESAURUS
C166533
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
MESH
C042631
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
EVMPD
SUB09171MIG
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
FDA UNII
22Z7E0X6OF
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
CAS
88058-88-2
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
SMS_ID
100000080324
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
ChEMBL
CHEMBL69271
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
CHEBI
177372
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
PUBCHEM
57533
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
EPA CompTox
DTXSID60236782
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY
INN
6101
Created by admin on Fri Dec 15 18:58:50 GMT 2023 , Edited by admin on Fri Dec 15 18:58:50 GMT 2023
PRIMARY