3 September 2018

Papaverine - the secret companion of morphine

Natural toxin

The phytotoxin papaverine is one representative of the isoquinoline alkaloid subclass, one of the biggest alkaloid groups with over 2500 known compounds. Papaverine is one of the major alkaloids commonly known as opiates, which also include the more famous morphine, thebaine and codeine.

Opiates, which are the first ever described plant alkaloids, are found in plants of the genus Papaver (poppy) belonging to the Papaveraceae family. In total, over 170 different alkaloids have been identified in Papaver species.

Papaver somniferum (P. somniferium or opium poppy) is one of about 80 species of the genus Papaver in the family Papaveraceae naturally occurring in the Mediterranean area. In Central Europe about nine different species are found, including the more common wild growing Papaver rhoeas (corn poppy or red poppy) which only contains weakly toxic rhoeadines. However, P. somniferium is grown as agricultural crop for the production of either poppy seeds, poppy seed oil or opium and other alkaloids for pharmaceutical purposes.

Since about 3000 BC, P. somniferium has been cultivated for its analgesic effect. Alkaloids as driver for the effect have only been identified in the early 19th century making the poppy alkaloids the first ever plant derived alkaloids described in literature. When wounded, all parts of the plant excrete a white liquid (latex) that shows the highest alkaloid content in the seed capsules while e.g., poppy seeds only contain less than 0.05%. Raw latex contains up to 30% of a varying alkaloid mixture with the main constituents being morphine (3-23%), codeine (0.2-3.5%) and papaverine (0.5-3%) depending on the species and growth conditions. The alkaloid content increases over the growth period reaching a maximum during flowering and generally in the early morning hours. Morning dew or rainfall can wash out alkaloids from ripe seed capsules with losses of up to 60-80%.

Structure of papaverine. Click image for interactive 3D-model

As a potential aquatic micropollutant, papaverine (CAS 58-74-2) has been recently categorized by Günthardt et al. as highly persistent (EPISuite predicted half-life >60 d) and, due to its ionization at average surface water pH, highly mobile (log Koc = 2.95, EPISuite experimental database) phytotoxin. However, due to its relatively low toxicity, papaverine may only pose a risk to aquatic organisms, when continually exceeding concentrations in the low mg/L range. As the growth of P. somniferium as a crop is highly restricted to just a few countries, regulations do even exist for growth in gardens with e.g., Germany only allowing 25 plants on an area of 10 m2, it is rather unlikely that those concentrations occur in the environment. However, it would be interesting to monitor papaverine occurrence in surface waters in areas of poppy growth for agricultural purposes as it is unknown what effects a wash out of alkaloids from poppy plants has on surface water quality. Altogether, the effect would be a result of the interactions of all alkaloids in the mixture and most likely be dominated by morphine.

SMILES: COC1=C(C=C(C=C1)CC2=NC=CC3=CC(=C(C=C32)OC)OC)OC

References:

  • Teuscher, E.; Lindequist, U. (2010) Biogene Gifte: Biologie-Chemie-Pharmakologie-Toxikologie. Wissenschaftliche Verlagsgesellschaft GmbH, Stuttgart, 3 Auflage.
  • Günthardt, B.F., et al.; Comprehensive Toxic Plants-Phytotoxins Database and Its Application in Assessing Aquatic Micropollution Potential. J. Agric. Food. Chem. 2018, 66 (29), 7577-7588.
  • ChemSpider, CSID:4518, http://www.chemspider.com/Chemical-Structure.4518.html (accessed Aug 22, 2018).

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