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| 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 | DopamineD2 andD3 receptoragonist;Antiparkinsonian agent |
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| Formula | C15H21NO2 |
| Molar mass | 247.338 g·mol−1 |
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Naxagolide (INNTooltip International Nonproprietary Name), also known asPHNO,dopazinol,L-647339, andMK-458 among other synonyms, is adopamine receptor agonist which was developed for the treatment ofParkinson's disease but was never marketed.[1][2][3][4] Aradiolabeled form has been used forbrain imaging.[5][3] The drug was developed for use bothorally andtransdermally.[4][6]
It acts as apotentdopamineD2 andD3 receptoragonist.[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-foldselectivity for the dopamine D3 receptor over the dopamine D2 receptor (Ki = 0.16 nM vs. 8.5 nM).[7] The drug is a naphthoxazinederivative.[6] It is structurally similar toergolines such aspergolide andcabergoline but is a non-ergoline itself.[10][9]
Naxagolide was first described in 1984 and was under development byMerck & Co in the 1980s and 1990s.[3][4] It was developed for treatment of Parkinson's disease and reachedphase 2clinical trials for this indication.[3] The drug was discontinued due to inadequate effectiveness and/or due totoxicity.[6][8]
PHNO (naxagolide, MK 458) [21], the most potent D2 agonist ever used, has been withdrawn because of animal toxicity, and this is also the case for mesulergin (CU 32 085), a D1 and D2 agonist.
Two non-ergot dopaminergic agonists were developed for the potential of transdermal administration. (+)4—Propyl-9-hydroxynaphthoxazine (PHNO; also known as MK-458 or naxagolide), perhaps the most potent dopaminergic compound, is readily absorbed through the skin. Although administration of PHNO in an oral sustained-release form showed antiparkinsonian effectiveness,147 this drug was discontinued from further development before the transdermal delivery route could be tested in human subjects.
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