Naxagolide

Naxagolide (INNTooltip International Nonproprietary Name), also known as PHNO, dopazinol, L-647339, and MK-458 among other synonyms, is a dopamine receptor agonist which was developed for the treatment of Parkinson's disease but was never marketed.^[1][2][3][4] A radiolabeled form has been used for brain imaging.^[5][3] The drug was developed for use both orally and transdermally.^[4][6]

Naxagolide

Clinical data
Other names	Dopazinol; Nazagolide; PHNO; (+)-PHNO; (+)-4-Propyl-9-hydroxynaphthoxazine; 4-Propyl-9-hydroxy-1,2,3,4a,5,6-hexahydronaphthoxazine; L-647339; L647339; MK-458; MK458
Routes of administration	Oral; Transdermal
Drug class	Dopamine D2 and D3 receptor agonist; Antiparkinsonian agent
Identifiers
IUPAC name (4aR,10bR)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-ol
CAS Number	88058-88-2
PubChem CID	57533
ChemSpider	51863
UNII	22Z7E0X6OF
ChEBI	CHEBI:177372
ChEMBL	ChEMBL69271
CompTox Dashboard (EPA)	DTXSID60236782
Chemical and physical data
Formula	C15H21NO2
Molar mass	247.338 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCN1CCO[C@H]2[C@H]1CCC3=C2C=C(C=C3)O
InChI 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 Key:JCSREICEMHWFAY-HUUCEWRRSA-N

It acts as a potent dopamine D₂ and D₃ receptor agonist.^[6][7] Naxagolide was described in the 1990s as the most potent dopamine D₂ receptor agonist that had been used.^[8][9] It shows about 50-fold selectivity for the dopamine D₃ receptor over the dopamine D₂ receptor (K_i = 0.16 nM vs. 8.5 nM).^[7] The drug is a naphthoxazine derivative.^[6] It is structurally similar to ergolines such as pergolide and cabergoline but is a non-ergoline itself.^[10][9]

Naxagolide was first described in 1984 and was under development by Merck & Co in the 1980s and 1990s.^[3][4] It was developed for treatment of Parkinson's disease and reached phase 2 clinical trials for this indication.^[3] The drug was discontinued due to inadequate effectiveness and/or due to toxicity.^[6][8]

See also

• Adrogolide
• Quinagolide