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MDO-NPA

MDO-NPA
Identifiers
  • 10,11-methylenedioxy-N-propylnoraporphine
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H21NO2
Molar mass307.393 g·mol−1
3D model (JSmol)
  • CCCN1CCC2=C3[C@H]1CC4=C(C3=CC=C2)C5=C(C=C4)OCO5
  • 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

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Pharmacokinetics

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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

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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

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References

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  1. ^ a b 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. ^ a b 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

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  • 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.