Plant Blog Post: Nightshade

Nightshade Toxicity

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The Basics (1)

Atropa Belladonna, commonly known as deadly nightshade, is one of the most poisonous plants in the world. It has shiny black berries that are sweet in flavor which can attract its unknowing victims. Ingestion of 10 berries for an adult and 3 berries for a child would be enough to see toxic effects.

  • Native to Europe, North Africa, and Western Asia
  • Belongs to the solanaceae family
    • Others in this family include potatoes, tomato, peppers, and eggplant
  • Also known as devil’s cherries, devil’s herb, divale, dwale, dwayberry, naughty man’s cherries, gray morel, and poison black cherry
  • The plant’s leaves, stems, berries, and roots all contain alkaloids that have been used as anticholinergics in FDA-approved drugs and homeopathic remedies.

Biotransformation (1)

  • S-(-)-Scopolamine (hyoscine) and S-(-)-hyoscyamine are biosynthesized from S-(-)-phenylalanine
  • Once ingested hyoscyamine is converted to atropine
    • A racemic mixture consisting of 50% l-hyoscyamine and 50% d-hyoscyamine

  (found here)

Toxicokinetics 

Scopolamine (2)

    • Mainly metabolized in the liver and eliminated in the urine. After oral administration, ~2.6% of unchanged scopolamine is recovered in urine
    • Half-life from oral administration is 63.7 ± 1.3 min

Atropine (3)

    • ~95% is bioavailable upon exposure
    • Much of the drug is destroyed by enzymatic hydrolysis
    • 13-50% of unchanged atropine is recovered in urine
    • Half-life is 3.0 ± 0.9 hours in adults

L-hyoscyamine (4)

    • Completely absorbed by sublingual and oral routes
    • Largely remains unmetabolized and excreted in the urine
    • Half-life is 3.5 hours

Mechanism of Action (1,5)

Scopolamine, atropine, and L-hyoscyamine act as competitive inhibitors of the muscarinic acetylcholine receptors (mAChRs) in the CNS. Scopolamine and atropine also have effects on parasympathetic post-ganglionic fibers and essentially turn off the parasympathetic drive at the target organ, which includes exocrine glands, smooth and cardiac muscle, and intramural neurons.

Scopolamine is the most potent of the three alkaloids, but atropine and L-hyoscyamine can produce similar effects at high doses.

Below is an acetylcholine receptor with mAChR depicted in thick black lines. The alkaloids bind to these receptors and inhibit them.

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Target organ (1)

  1. Central Nervous System: muscarinic acetylcholine receptors
  2. Peripheral Nervous System: post-ganglionic fibers located in exocrine glands, smooth and cardiac muscle, and intramural neurons

Historical Uses (1,6)

  • During the medieval period, nightshade was widely used by witches, sorcerers, and professional prisoners
  • Ancient Romans used the plant to make poison-tipped arrows
  • In the 16th and 17th centuries, herbalists and apothecaries began to study and use the plant
  • In the 20th century, nightshade began being abused for its hallucinogenic effects across the Eastern Hemisphere

Signs and Symptoms of Toxicity (1,5)

The effects of belladonna alkaloids are dose-dependent

CNS symptoms:

    • Confusion, bizarre behavior, hallucinations, memory dysfunction, and cardiovascular and respiratory failure

PNS symptoms:

    • Tachycardia, hypertension, dry mouth, flushed skin, fever, dilated pupils, constipation, and urinary retention

Treatments (1)

  • Gastrointestinal decontamination, or gastric lavage, is commonly used to wash out the stomach with a solution that neutralizes the atropine
  • Benzodiazepines are used in cases of agitation, delirium, tachycardia, and seizures to sedate the patient
  • Physostigmine, a reversible cholinesterase inhibitor that acts on both the PNS and CNS, can be considered in life-threatening cases such as those with profound tachycardia, severe hyperthermia, and unmanageable agitation
    • Physostigmine has the potential to cause seizures and cardiac arrhythmia and should be used with caution

Biomarkers 

There are no biomarkers for nightshade toxicity.

References:

  1. Kwakye, Gunnar F., Jennifer Jiménez, Jessica A. Jiménez, and Michael Aschner. “Atropa Belladonna Neurotoxicity: Implications to Neurological Disorders.” Food and Chemical Toxicology 116 (2018): 346-53. Print.
  2. “Scopolamine.” Uses, Interactions, Mechanism of Action | DrugBank Online. Web. 23 July 2021.
  3. “Atropine.” Uses, Interactions, Mechanism of Action | DrugBank Online. Web. 23 July 2021.
  4. “Hyoscyamine.” Uses, Interactions, Mechanism of Action | DrugBank Online. Web. 23 July 2021.
  5. Watkins, John B., III. “Toxic Effects of Plants and Animals.” Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th edition Ed. Curtis D. Klaassen. McGraw Hill, 2019, https://accesspharmacy-mhmedical-com.proxy.lib.ohio-state.edu/content.aspx?bookid=2462&sectionid=202677479.
  6. Largo, Michael. “The A-List Celebrity of Poisonous Plants.” Slate Magazine. Slate, 18 Aug. 2014. Web. 23 July 2021.