Cytisine - a quinolizidine alkaloid – University of Copenhagen

NaToxAq > Toxin of the week > Cytisine

24 June 2019

Cytisine - a quinolizidine alkaloid

Natural toxin

A teratogenic, respiratory stimulant (with nicotine-like activity) and a hallucinogenic alkaloid.

Quinolizidine alkaloid contains two fused 6-membered rings that share nitrogen. Naturally, they are found as the N-oxides as well as the free bases. They are isolable from a number of well-known shrubs and trees such as broom, laburnum and gorse. They have been responsible for much accidental poisoning in sheep, cattle and humans from the consumption of such plants, and particularly their seeds. For instance, cytisine is more acutely toxic and can cause damage in livestock due to its teratogenic effect.

Cytisine, also known as baptitoxine and sophorine, is a prevalent plant based alkaloid found in many members of the Fabaceae family such as Laburnum, Sophor and, Baptisia. For instance, it constitutes 1-5% of the seeds of the common garden decorative plant Laburnum anagyroides (Cytisus laburnum; Golden Rain accacia, Fig 1). Its concentration varies depending on parts of the plant, maturation state of the plant and climate condition. Cytisine is described as the toxic principle of this plant.

Cytisine is easily soluble in water, chiroform and ethanol. It has relatively rigid conformation composed of an unsymmetrical, partially aromatic and bridged tricyclic skeleton.

Figure 1: Cytisus laburnum L. plant (left) and chemical structure of cytisine (right). Click figure for interactive 3D structure

Cytisine is a highly toxic alkaloid and readily absorbs in the gastrointestinal tract and distribute to the liver, adrenalin gland and kidney. A number of poisoning in humans and animals has been reported following ingestion of seeds of C. Laburnum, which contains cytisine. It showed teratogenic effect in rabbits and poultry. It is a respiratory stimulant, with nicotine-like activity, and a hallucinogenic. However, pharmacologically, cytisine appears to be a potential therapeutic utility in aiding smoking cessation. In addition, it has shown analgesic, antihypertensive, inotropic, antispasmodic, antioxidant, and insecticidal activities.

The poisoning symptom with cytisine are nausea, vomiting, convulsion, headache and, in large doses, even death via respiratory failure. The effects of toxic doses include weakness, dizziness, impairment of motor coordination, muscular facial twitches, increased reflex sensitivity, mydriasis, shallow breathing, occasional urinary retention, and ultimately, tonic-clonic convulsions followed by collapse and coma with respiration cessation, mainly caused by paralysis of respiratory muscles.

CAS NO: 485-35-8
Chemical Formula: C11H14N2O
SMILES: C1C2CNCC1C3=CC=CC(=O)N3C2

References:

  • Harborne JB, Baxter H and Moss GP (1999). Phythochemical dictionary: a hand book of bioactive compounds from plants. Second edition, TJ International Ltd, Padstow, UK.
  • Rouden J, Lasne MC, Blanchet J, and Baudoux J (2014). Review: (−)-Cytisine and Derivatives: Synthesis, Reactivity, and Applicationserome. Chem. Rev. 114: 712−778.
  • Tutka P, Zatoñski W (2006). Review - Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy. Pharmacological reports 58,777-798.
  • Boido CC, Sparatore F (1999). Synthesis and preliminary pharmacological evaluation of some cytisine derivatives. Farmaco, 1999, 54, 438–451.

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