MDO-NPA

MDO-NPA

Identifiers
IUPAC name (12R)-10,11-Methylenedioxy-N-propylnoraporphine
CAS Number	81264-57-5 113678-73-2
PubChem CID	133642
ChemSpider	117885
ChEMBL	ChEMBL4470553
CompTox Dashboard (EPA)	DTXSID201001887
Chemical and physical data
Formula	C20H21NO2
Molar mass	307.393 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCN1CCC2=C3[C@H]1CC4=C(C3=CC=C2)C5=C(C=C4)OCO5
InChI InChI=1S/C20H21NO2/c1-2-9-21-10-8-13-4-3-5-15-18(13)16(21)11-14-6-7-17-20(19(14)15)23-12-22-17/h3-7,16H,2,8-12H2,1H3/t16-/m1/s1 Key:YSONYEIWWIFWEV-MRXNPFEDSA-N

MDO-NPA (10,11-methylenedioxy-N-n-propylnoraporphine) is a synthetic aporphine derivative used as a research tool in neuropharmacology. It was developed as a methylenedioxy prodrug of N-n-propylnorapomorphine (NPA). A noteworthy advantage that the MDO-NPA congener has over NPA and apomorphine is that MDO-NPA has a high oral bioavailability, whereas the other two do not and must be delivered via subcutaneous injection or intraperitoneally.

Pharmacology

Pharmacokinetics

In vivo O-dealkylation releases NPA, yielding an orally effective, relatively long-acting dopaminergic agent that acts at central dopamine receptors. Evidence for this prodrug behavior includes blockade of MDO-NPA’s behavioral effects and prevention of NPA formation by the microsomal oxidase inhibitor SKF-525A. ^[1]

Pharmacodynamics

In animal models, MDO-NPA produces robust dopamine-mediated behavioral effects with “depot-like” properties, and across studies has shown dose-dependent agonist/antagonist interactions and, for certain stereoisomers, limbic-selective actions. ^{[1] [2]} MDO-NPA exists as two distinct enantiomers. One of these enantiomers is active as a dopamine agonist while the other is active as a dopamine antagonist. ^[3]

MDO-NPA has not been developed as a therapeutic drug and remains primarily of experimental interest alongside related aporphine congeners. ^[2]

See also

• MDMA
• MDA
• Propylnorapomorphine
• UWA-001
• Piribedil
• Anonaine

References

1. Campbell A, Baldessarini RJ, Ram VJ, Neumeyer JL (October 1982). "Behavioral effects of (-)10,11-methylenedioxy-N-n-propylnoraporphine, an orally effective long-acting agent active at central dopamine receptors, and analogous aporphines". Neuropharmacology. 21 (10): 953–61. doi:10.1016/0028-3908(82)90106-x. PMID   6890636.
2. Anlezark GM, Blackwood DH, Meldrum BS, Ram VJ, Neumeyer JL (1983). "Comparative assessment of dopamine agonist aporphines as anticonvulsants in two models of reflex epilepsy". Psychopharmacology. 81 (2): 135–9. doi:10.1007/BF00429007. PMID   6415743.
3. Baldessarini RJ, Neumeyer JL, Campbell A, Sperk G, Ram VJ, Arana GW, et al. (January 1982). "An orally effective, long-acting dopaminergic prodrug:(−)-10, 11-methylenedioxy-N-propylnoraporphine". European Journal of Pharmacology. 77 (1): 87–88. doi:10.1016/0014-2999(82)90543-X. PMID   6277658.

Further reading

• Ram VJ, Neumeyer JL (1988). "Synthesis of R(-)- and S(+)-10,11-methylenedioxy-N-(n-propyl)noraporphines". Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry. 27 (1–12): 947–949.
• Baldessarini RJ, Neumeyer JL, Campbell A, Sperk G, Ram VJ, Arana GW, et al. (January 1982). "An orally effective, long-acting dopaminergic prodrug: (-)-10,11-methylenedioxy-N-propylnoraporphine". European Journal of Pharmacology. 77 (1): 87–88. doi:10.1016/0014-2999(82)90543-X. PMID   6277658.
• Campbell A, Baldessarini RJ, Kula NS, Ram VJ, Neumeyer JL (February 1987). "S(+)methylenedioxy-N-n-propylnoraporphine: an orally active inhibitor of dopamine selective for rat limbic system". Brain Research. 403 (2): 393–397. doi:10.1016/0006-8993(87)90083-7. PMID   3828830.