Chemistry:MDO-NPA
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
References
- ↑ 1.0 1.1 "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. October 1982. doi:10.1016/0028-3908(82)90106-x. PMID 6890636.
- ↑ 2.0 2.1 "Comparative assessment of dopamine agonist aporphines as anticonvulsants in two models of reflex epilepsy". Psychopharmacology 81 (2): 135–9. 1983. doi:10.1007/BF00429007. PMID 6415743.
- ↑ "An orally effective, long-acting dopaminergic prodrug:(−)-10, 11-methylenedioxy-N-propylnoraporphine.". European Journal of Pharmacology 77 (1): 87–88. January 1982. doi:10.1016/0014-2999(82)90543-X. PMID 6277658.
Further reading
- "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. 1988.
- "An orally effective, long-acting dopaminergic prodrug: (-)-10,11-methylenedioxy-N-propylnoraporphine". European Journal of Pharmacology 77 (1): 87–88. January 1982. doi:10.1016/0014-2999(82)90543-X. PMID 6277658.
- "S(+)methylenedioxy-N-n-propylnoraporphine: an orally active inhibitor of dopamine selective for rat limbic system". Brain Research 403 (2): 393–397. February 1987. doi:10.1016/0006-8993(87)90083-7. PMID 3828830.
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