Yo! GABA GABA and Other Key Players in "Natural" Seizures

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Yo! GABA GABA and Other Key
Players in "Natural" Seizures
Christina H. Hernon, MD, University of Massachusetts Memorial Hospital,
Worcester, MA
Brian J. Wolk, MD, Loma Linda University Medical Center, Loma Linda, CA
Objectives:
Appreciate the variety of mechanisms of natural toxin-induced seizures and how
they interact
Be able to visually identify at least 5 natural toxins causing seizures
Be able to describe the mechanism of seizures in at least 5 natural toxins
Disclosures:
Dr. Wolk is a Co-investigator for Analatro (Black Widow Fab2 Antivenom)
-Instituto Bioclon/Rare Disease Therapeutics
Help, I just had a
seizure in my
hand!
Horrible Herbs
Yo! GABA
GABA
Look-a-likes
That wasn’t a
seizure; that was
a dance move
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Category 1 questions follow
Question
The primary mechanism of the toxin found in this
substance.
http://www.flickr.com/photos/bonjourwill/4528624762/sizes/o/
Answer
Adenosine receptor antagonism
Question
Rick James may have used
a certain substance
derived from this plant:
Answer
Coca Plant
Coca Picture Refernce: http://upload.wikimedia.org/wikipedia/commons/7/72/Colcoca04.jpg
Question
This plant native to
Southeast Asia:
Hint: commonly used
to ‘stun’ fish
Answer
Plant: Anamirta cocculus or Fishberries
Picture Reference:
http://upload.wikimedia.org/wikipedia/commons/7/70/Anamirta_cocculus_02.JPG
Question
This toxin is derived from a large tree with broadleaves.
It is native to China and Japan, but is considered an
invasive species in the Southern United States.
Answer
http://i00.i.aliimg.com/photo/v0/105180782/Camphor_Bulk.jpg
Camphor
http://plants.ifas.ufl.edu/misc/reco_cards/cincam.pdf
Question
Latin name for the genus, toxin
and mechanism of toxicity:
Answer
Aconitum, Aconitine, & Sodium-Channel Blockade
Also known as Wolfsbane or Monskhood
Picture Reference: http://upload.wikimedia.org/wikipedia/commons/7/70/Aconitum_napellus_Ticino.jpg
Category 2 questions follow
Question
http://farm9.staticflickr.com/8301/7808736868_5ce5abf011_b.jpg
Creative Commons License
Plant and mechanism
of action of its toxin:
Answer
Tobacco/Nicotinic
Question
This bane of livestock is terribly toxic.
Answer
Cowbane or Cicuta Virosa
Question
This edible ‘pea’ contains the neurotoxin ẞ-Noxalylamino-L-alanine (BOAA) which is a glutamate
agonist
Answer
Lathyrus Sativa (Chickling Pea)
Question
This fall flower may give
you seizures, but that could
be the least of your
problems:
http://s0.geograph.org.uk/photos/54/59/545962_fd7cb876.jpg
“© Copyright Evelyn Simak and licensed for reuse under this Creative Commons
Licence.”
Answer
Colchicum autumnale/autumn crocus (Colchicine)
Question
This relative of water hemlock
from the island of Sardinia may
give you a Sardonic Grin:
Answer
Oenanthe fistulosa (Water Dropwort)
http://commons.wikimedia.org/wiki/File:Illustratio
n_Oenanthe_aquatica0.jpg
Category 3 questions follow
Question
How does cocaine cause seizures?
farm3.staticflickr.com/2190/2170100460_2094dd2d6d_o.jpg
http://
Answer
Adrenergic/Sympathomimetic stimulation
Question
The antidote for
ingestion of this savory
shroom:
Answer
Pyridoxine
-Gyromitrin metabolized to Monomethylhydrazine
Picture Reference: http://upload.wikimedia.org/wikipedia/commons/9/97/Fr%C3%BChjahrslorchel.JPG
Question
Before Redbull and Vodka, you
could get your uppers &
downers from a drink made
with this plant:
Answer
Artemisia absinthium or Wormwood
Picture Reference: http://upload.wikimedia.org/wikipedia/commons/f/f5/Artemisia_absinthium_0002.JPG
Question
Mechanism of this toxin found
in mussels; linked to severe
permanent neurologic damage
and the deaths of > 400 Sea
Lions:
http://cleanfish.com/system/images/BAhbB1sHOgZmIjsyMDExLzAzLzIxLzE2LzUwL
zMyLzMxMS9TYWx0U3ByaW5nX011c3NlbHNfV2hvbGVfOC5qcGdbCDoGcDoKdGh
1bWIiDTQ1MHg0NTA+/SaltSpring_Mussels_Whole_8.jpg
Answer
Glutamate Analogue/NMDA Agonist
Picture Reference: Figure 1 in Teitelbaum JS, Zatorre RJ, Carpenter S, Gendron D, Evans AC, Gjedde A, et al. Neurologic
sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. The New England journal of medicine.
1990;322(25):1781-7.
Question
The toxin and mechanism, respectively, of Anamirta
cocculus
Answer
Toxin:
Picrotoxin
Mechanism:
GABA inhibitor (non-competitive)
May also inhibit glycine receptors
Category 4 questions follow
Question
Socrates did NOT eat this:
Answer
Cicuta Maculata (Water Hemlock)
Picture Reference: http://www.illinoiswildflowers.info/wetland/photos/wt_hemlock1.jpg
Question
This “false” fungus may be “tasty” but ingestion is
inadvisable
Answer
Gyromitra Esculenta or the False Morel
Question
The flowers of this plant
may resemble the pants of
a person from a Northern
European country; this
plant may also cause
seizures in livestock:
http://farm5.staticflickr.com/4015/4525160667_8fb31c049c_b.jpg Creative
Commons License
Answer
Dicentra cucullaria/Dutchman's breeches
Toxin: Bicuculline
Question
This bad actor causes seizures less frequently
than its cousin, and may be identifiable by its
coloration:
http://farm1.staticflickr.com/208/508080682_a19188ceb5_o.jpg Creative Commons License
Answer
Conium maculatum or Poison Hemlock
Question
This stellate assassin is
sometimes mistaken for its
benign Chinese cousin:
Answer
http://upload.wikimedia.org/wikipedia/commons/6/62/
Illicium_verum_2006-10-17.jpg
Illicium anisatum/Japanese star anise
(Anisatin)
For comparison:
Illicium verum or
Chinese Star Anise
(Non-toxic)
-non-competitive GABA (channel)
inhibition
Picture Reference: http://2.bp.blogspot.com/_a5abCT2isic/TBl3SSBhWQI/AAAAAAAACwM/P63cuGW_gzc/s400/star_anise.jpg
Category 5 questions follow
Question
The NMDA agonist in this fungus theoretically could
causes seizures, but rarely does due to it’s
concomitant CNS depressant
Answer
Amanita Muscaria or Fly agaric
Question
The name of the NMDA agonist
in this mushroom:
http://s0.geograph.org.uk/geophotos/02/12/31/2123114_83948608.jpg
“© Copyright JamesB and licensed for reuse under this Creative Commons Licence.”
Answer
Ibotenic Acid
Question
Chew on this, and
you might get a
little rush:
Answer
Qat or Khat (Cathinones)
Question
Found in some traditional remedies, this toxin may
give you a convulsion to remember
Answer
Strychnos Nux Vomica or
Strynchine
Question
Specific mechanism by
which this cellular
asphyxiant may cause
seizures (other than general
cellular asphyxia):
http://upload.wikimedia.org/wikipedia/commons/9/9e/Autumn_Red_peaches.jpg
Answer
Glutamic Acid Decarboxylase Inhibition

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