26 November 2018

Digoxin – the cardenolide that may give you van Gogh’s “yellow vision”

NATURAL TOXIN. In the final years of Vincent van Gogh’s life, this Dutch post-impressionist showed an undisguised fondness of using bright yellow in his many paintings such as The Night Café (1888), Les pissenlits (1889) and Sunflowers series (1887-1889). One speculation is that the artist’s color perception may be affected by over-medication with digitalis. The plant was prescribed by his physician Dr. Paul Gachet as a treatment for epilepsy, whereas the patient tented to get xanthopsia, a yellow bias in vision, after receiving large and repeated doses.

Fig 1. Portrait of Dr. Gachet by Vincent van
Gogh (1853-1890). The digitalis flowers in
the vase are thought to account for the
artist's love of 'high yellow palette'.

Digitalis (also known as “foxglove”) is a genus that comprises 23 species of biennial or perennial herbs. They naturally occur in Europe, western and central Asia, and northwestern Africa. The flowers are tube-like, blooming in colors from white to purple, pink, lavender and yellow, with dark spots inside the blooms. The roots, sap, flowers, pollen, seeds and leaves are all poisonous. Highest toxin contents are always found in leaves.

For a long time period in history extracts of Digitalis have been widely used in folk medicine for heart diseases and psychiatric disorders. The toxic and medical qualities were first documented in 1785 by the English physician William Withering. During the two world wars, tons of Digitalis purpurea leaves were harvested in Britain to produce drugs. After WWII, the cultivation and breeding of Digitalis lanata was promoted in Netherland with the Aid funds; the dried plants were exported to Britain, Germany, France and the United States.

Fig 2. Left and middle: Digitalis lanata Ehrh. cultivated as a crop. Right: At medical market digoxin is sold under brand name LANOXIN. Click image for an interactive 3D model of digoxin.

Nowadays Digitalis lanata is still of economic interest in European pharmaceutical industry for its production of digoxin (CAS 20830-75-5). The isolated pure compound is odorless white crystals, melting and decomposing at above 230°C. It has a water solubility of 0.065 mg/mL at 25°C and LogP of 1.26 (HMDB). Like other cardiac glycosides, digoxin acts as an inhibitor of the  Na/K-ATPase with specific effects on the myocardium. It is on the WHO’s list of Essential Medicines among other cardiovascular medicines, commercially available under the brand name  LANOXIN. Meanwhile, risk of intoxication is common owning to the narrow therapeutic index. Symptoms include nausea, vomiting, diarrhea, xanthopsia, irregular heartbeat and death at the worst case.


References and Figures: