Aporphine

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Aporphine
Chemical structure of aporphine
Names
IUPAC name
6-Methyl-5,6,6a,7-tetrahydro-4H-dibenzo(de,g)quinoline
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
Properties
C17H17N
Molar mass 235.324 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Aporphine is one of a class of quinoline alkaloids. Many different relatives of this compound have been purified from plants.[1] Many water-lillies (Nymphaea species) produce aporphine alkaloids, like nymphaeine, nymphaline, nupharine, alfa- and beta-nupharidine[2]. Aporphines from other plants include some that occur in extracts of Cassytha species that have been used in African folk medicine to treat cancer and trypanosomiasis. In vitro tests of some of the aporphines from Cassytha filiformis, namely actinodaphnine, cassythine, and dicentrine, on Trypanosoma brucei did show promising levels of activity. Investigation of possible mechanisms revealed that the active compounds bind to DNA and act as intercalating agents, besides inhibiting topoisomerase activity[3]

Aporphine is a 5-HT1a partial agonist with a ki of 80nM and a 5-HT7 antagonist with a ki of 88nM.[4] Aporphine is a Dopamine D1 antagonist with a ki of 717nM[5] and a dopamine D2 antagonist with a ki of 527nM.[6] Aporphine and its related alkaloids bulbocapnine, boldine, glaucine and corytuberine are antipsychotic, exert naloxone-reversible antinociceptive activity and with the exception of corytuberine are anticonvulsant.[7] Some derivatives of aporphine such as S(+)-N-propylnorapomorphine have potential as low side effect profile antipsychotics. S(+)-N-propylnorapomorphine is highly selective for meso-limbic dopaminergic tracts and function as efficacious partial agonists, with no elevation in prolactin.[8]

See also[edit]

References[edit]

  1. ^ Stévigny, C.; Bailly, C.; Quetin-Leclercq, J. (2005). "Cytotoxic and antitumor potentialities of aporphinoid alkaloids". Current medicinal chemistry. Anti-cancer agents. 5 (2): 173–182. doi:10.2174/1568011053174864. PMID 15777224. 
  2. ^ Oliver-Bever B., 1983, Medicinal plants in tropical West Africa II. Plants acting on the nervous system, Journal of Ethnopharmacology, vol. 7, pp. 1-93.
  3. ^ Hoet, Sara; Stévigny, Caroline; Block, Sébastien; Opperdoes, Frederik; Colson, Pierre; Baldeyrou, Brigitte; Lansiaux, Amélie; Bailly, Christian; Quetin-Leclercq, Joëlle Alkaloids from Cassytha filiformis and Related Aporphines: Antitrypanosomal Activity, Cytotoxicity, and Interaction with DNA and Topoisomerases. Planta Med 2004; 70(5): 407-413. DOI: 10.1055/s-2004-818967
  4. ^ Leopoldo M, Lacivita E, Berardi F, Perrone R, Hedlund PB (February 2011). "Serotonin 5-HT7 receptor agents: Structure-activity relationships and potential therapeutic applications in central nervous system disorders". Pharmacology & Therapeutics. 129 (2): 120–48. doi:10.1016/j.pharmthera.2010.08.013. PMC 3031120Freely accessible. PMID 20923682. 
  5. ^ Hedberg MH, Linnanen T, Jansen JM, et al. (August 1996). "11-substituted (R)-aporphines: synthesis, pharmacology, and modeling of D2A and 5-HT1A receptor interactions". Journal of Medicinal Chemistry. 39 (18): 3503–13. doi:10.1021/jm960189i. PMID 8784448. 
  6. ^ Linnanen T, Brisander M, Unelius L, et al. (April 2001). "Atropisomeric derivatives of 2',6'-disubstituted (R)-11-phenylaporphine: selective serotonin 5-HT(7) receptor antagonists". Journal of Medicinal Chemistry. 44 (9): 1337–40. doi:10.1021/jm0108505. PMID 11311055. 
  7. ^ Zetler G (1988). "Neuroleptic-like, anticonvulsant and antinociceptive effects of aporphine alkaloids: bulbocapnine, corytuberine, boldine and glaucine". Archives Internationales de Pharmacodynamie et de Thérapie. 296: 255–81. PMID 2907279. 
  8. ^ Baldessarini RJ, Campbell A, Ben-Jonathan N, Ellingboe J, Zong R, Neumeyer JL (August 1994). "Effects of aporphine isomers on rat prolactin". Neuroscience Letters. 176 (2): 269–71. doi:10.1016/0304-3940(94)90098-1. PMID 7830962.