Dopamine → Morphine

HRID 447707

Reaktionsgleichung

Reaktionsgleichung von HRID 447707
NCCC1C=CC(O)=CC=1.NCCC1C=CC(O)=C(O)C=1.COC1C=CC2N=CC=C([C@H](O)[C@@H]3N4C[C@H](C=C)C(CC4)C3)C=2C=1.[CH3:46][N:47]1[CH:56]([CH2:57][C:58]2[CH:59]=[CH:60][C:61]([O:65]C)=[C:62]([OH:64])[CH:63]=2)[C:55]2[CH:54]=[C:53](O)[C:52]([O:68]C)=[CH:51][C:50]=2[CH2:49][CH2:48]1.CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5[C@@H](O)C=C[C@@H]2[C@]5(C=34)CC1>>[CH:59]1[C:58]2[CH2:57][C@H:56]3[N:47]([CH2:48][CH2:49][C@@:50]45[C@H:55]3[CH:54]=[CH:53][C@H:52]([OH:68])[C@@H:51]4[O:64][C:62]([C:63]=25)=[C:61]([OH:65])[CH:60]=1)[CH3:46]

Komponenten

6

Edukt 5

HCID 681Dopamine5×HCID 5610Tyramine3×HCID 5953(S)-[(2R,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol2×HCID 102331-((3-Hydroxy-4-methoxyphenyl)methyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-olHCID 5284371Codeine

Produkt 1

HCID 5288826Morphine

Versuchsvorschrift

To examine the tyramine to dopamine step, dopamine (DA) levels in ganglia and hemolymph were examined before and after tyramine addition followed by CYP2D6 inhibition by quinidine. Tyramine injection significantly increased ganglionic (4.98±0.27 μg/g to 9.17±1.21 μg/g wet weight; P<0.01) and hemolymph (10.13±1.24 μg/mL to 16.47±1.28 μg/mL, P<0.05) DA levels (FIGS. 19 and 20). The ganglionic and hemolymph DA level increases were blocked by quinidine exposure, demonstrating that the CYP2D6 enzyme was mediating this step. Ganglia were also exposed to THP, reticuline, DA, or codeine. Each resulted in significantly enhanced morphine levels, a phenomenon that was also significantly blocked by quinidine exposure, again demonstrating a role for CYP2D6 in the second part of the morphine biosynthetic pathway (FIGS. 15 and 20).

Quellen und Nachweise

ORD-Eintrag
ord-eae22b0c7c294073beeb048fda45eec6
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481559B2

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