07 October 2019

Gelsemine - from yellow jasmine and Arthur Conan Doyles' self-poisoning experience

Gelsemine is the main alkaloid

in Gelsemium sempervirens Ait. (aslo known as yellow jasmine), and it is native to the southwest United States.

This plant also grows in Mexico and parts of Central America. At least 120 alkaloids have been isolated and identified from genus Gelsemium. Gelsemine is one of the predominant alkaloids together with koumine, gelsemicine, gelsenicine, gelsedine, sempervirine, koumidine, koumicine and humantenine [2].

I feel convinced that I could have taken as much as half an ounce of the tincture, had it not been for the extreme diarrhoea it brought on.
-Believe me, yours sincerely,
A. C. D.
Clifton House, Aston Road, Birmingham [1].

 
Gelsemium sempervirens Ait

This alkaloid was isolated from G. sempervirens Ait. in 1876, but its structure was determined in 1959 by means of nuclear magnetic resonance spectroscopic techniques and X-ray crystallographic analysis. Gelsemine contains a hexacyclic cage structure and seven contiguous chiral carbon centres [3].

Due to complex structural features and different biological effects, these alkaloids have drawn attention of chemists and pharmacologists [2]. Sir Arthur Conan Doyle himself was studying primary symptoms of gelsemine overdose, while he was a student at the University of Edinburgh Medical School. In the conclusion of “Gelseminum as a Poison” in the British Medical Journal, Doyle mentions that a healthy adult may take up to 90 minims (1 minim = 1 drop = 0.06 mL), however from 90 to 120 drops causes weakness, vertigo and partial paralysis of the ciliary muscle. At 150 drops, headache, diarrhoea and extreme lassitude appears. He believed that it is possible to tolerate these effects, like with opium [1].

Gelsemine activates the spinal glycine receptors, which reduce sensitivity to pain. Glycine receptor slows down neurotransmission in the spinal cord, brain stem, caudal brain and retina, and controls different motor and sensory functions (visual, auditory and pain processing). In animal models, gelsemine demonstrated effectiveness towards treatment of both neurotic pain (occurs due to lesions in nervous system) and sleep disturbance in mice [2, 4, 5].

Gelsemine and strychnine have the same indole ring and functional groups such as the amide, tertiary amine, spirocyclic and cyclic ether groups. Recent study confirms that gelsemine and strychnine bind to the glycine receptor at the same site [2].

References

  1. Doyle, A.C., Gelseminum as a Poison. British Medical Journal 1879: p. 483.
  2. Zhang, J.-Y. and Y.-X. Wang, Gelsemium analgesia and the spinal glycine receptor/allopregnanolone pathway. Fitoterapia, 2015. 100: p. 35-43.
  3. Chen, X., et al., Total synthesis of (+)-gelsemine via an organocatalytic Diels–Alder approach. Nature Communications, 2015. 6(1): p. 7204.
  4. Brower, J. Gelsemium and Sir Arthur Conan Doyle, the Self-Poisoner. 2014; Available from: https://naturespoisons.com/.
  5. Wu, Y.-e., et al., Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice. Acta Pharmacologica Sinica, 2015. 36(11): p. 1308-1317.

Pictures

  • Both from Zhang et al.