127
8
traditional methods of preparing curare from plants by natives (Bonpland et al. 1814).
While curare kills animals that were wounded by poisoned arrows very quickly, the prey
is safe to eat due to very low resorption of tubocurarine and other curare alkaloids in the
gastrointestinal tract. This property of curare was already described by Humboldt, who
tested it by drinking the plant extract unharmed. Nevertheless, it should take more than
100 years before curare became a muscle relaxant during surgery in Western medicine
(Czarnowski et al. 2007).
The Strychnos nux-vomica tree also belongs to the genus Strychnos, and it is the
source of strychnine, a terpenoid indole alkaloid that targets both, the nicotinic acetylcholine receptor and the ionotropic glycine receptor and which is described in the context of the latter in 7 Sect. 8.4.
Some cyanobacteria produce the nicotinic acetylcholine receptor agonist anatoxin A.
This tropane-related alkaloid is also known as the “very fast death factor” due to its strong
neurotoxicity (Tufariello et al. 1984). It is produced by a number of species of cyanobacteria and can poison drinking water. It was only discovered in the 1960s when the poisoning
of cattle by water from the Saskatchewan Lake in Canada was investigated. Since its discovery, it was determined as the cause for multiple death of cattle or other animals such as
dogs (Edwards et al. 1992). The largest death toll so far ascribed at least in part to the
action of anatoxin A was the death of about 30,000 flamingos on lake Bogoria in Kenia in
the autumn of 1999 (Krienitz et al. 2003). Anatoxin A is only one of the cyanobacteriaderived substances that make toxic harmful algae blooms so dangerous, but it is believed
to be the major cause of neurotoxic blooms (Rapala et al. 1993). Prevention of grazing was
suggested as one potential role of these algae toxins; however, allopathy could be another
factor. Indeed, it was shown that anatoxin A synthesis is increased in the presence of the
green alga Chlamydomonas reinhardtii, and it can inhibit the mobility of this organism
(Holland and Kinnear 2013). However, very little is generally known about the natural
role of cyanobacterial toxins.
8.3 GABA A Receptors: Thujone, Cicutoxin and Anisatin
The best known secondary metabolites affecting GABA A receptors again come from
mushrooms (. Fig. 8.4). Muscimol, a isoxazole alkaloid, is the actual psychoactive compound that is responsible for the effect of Amanita muscaria intoxication. Ibotenic acid is
also found in Amanita muscaria and related species of mushroom but only serves as a
prodrug to muscimol. However, since it is decarboxylated to muscimol upon digestion, it
has the same effect during human consumption of these mushrooms.
GABA-active plant products include sesquiterpenes such as valerenic acid found in
valerian (Valeriana officinalis) or monoterpene ketones like camphene found in
Cinnamomum camphora. A more infamous plant-derived antagonist of the GABA A receptor is the monoterpene ketone thujone found in plants such as thuja, Nootka cypress,
mugwort, oregano, common sage, tansy or wormwood. Thujone has a menthol odour and
is best known as a component of Absinthe (see 7 Box 8.3), which contains extracts of the
grand wormwood, Artemisia absinthium. Thujone is considered as an addictive psychoactive drug and its use in food and drinks is therefore limited by law. In the European Union,
up to 35 mg/kg thujone is permitted for alcoholic beverages prepared from Artemisia
species with stronger limits for food and non-alcoholic beverages. Similar restrictions
8.3 · GABA A Receptors: Thujone, Cicutoxin and Anisatin
8
traditional methods of preparing curare from plants by natives (Bonpland et al. 1814).
While curare kills animals that were wounded by poisoned arrows very quickly, the prey
is safe to eat due to very low resorption of tubocurarine and other curare alkaloids in the
gastrointestinal tract. This property of curare was already described by Humboldt, who
tested it by drinking the plant extract unharmed. Nevertheless, it should take more than
100 years before curare became a muscle relaxant during surgery in Western medicine
(Czarnowski et al. 2007).
The Strychnos nux-vomica tree also belongs to the genus Strychnos, and it is the
source of strychnine, a terpenoid indole alkaloid that targets both, the nicotinic acetylcholine receptor and the ionotropic glycine receptor and which is described in the context of the latter in 7 Sect. 8.4.
Some cyanobacteria produce the nicotinic acetylcholine receptor agonist anatoxin A.
This tropane-related alkaloid is also known as the “very fast death factor” due to its strong
neurotoxicity (Tufariello et al. 1984). It is produced by a number of species of cyanobacteria and can poison drinking water. It was only discovered in the 1960s when the poisoning
of cattle by water from the Saskatchewan Lake in Canada was investigated. Since its discovery, it was determined as the cause for multiple death of cattle or other animals such as
dogs (Edwards et al. 1992). The largest death toll so far ascribed at least in part to the
action of anatoxin A was the death of about 30,000 flamingos on lake Bogoria in Kenia in
the autumn of 1999 (Krienitz et al. 2003). Anatoxin A is only one of the cyanobacteriaderived substances that make toxic harmful algae blooms so dangerous, but it is believed
to be the major cause of neurotoxic blooms (Rapala et al. 1993). Prevention of grazing was
suggested as one potential role of these algae toxins; however, allopathy could be another
factor. Indeed, it was shown that anatoxin A synthesis is increased in the presence of the
green alga Chlamydomonas reinhardtii, and it can inhibit the mobility of this organism
(Holland and Kinnear 2013). However, very little is generally known about the natural
role of cyanobacterial toxins.
8.3 GABA A Receptors: Thujone, Cicutoxin and Anisatin
The best known secondary metabolites affecting GABA A receptors again come from
mushrooms (. Fig. 8.4). Muscimol, a isoxazole alkaloid, is the actual psychoactive compound that is responsible for the effect of Amanita muscaria intoxication. Ibotenic acid is
also found in Amanita muscaria and related species of mushroom but only serves as a
prodrug to muscimol. However, since it is decarboxylated to muscimol upon digestion, it
has the same effect during human consumption of these mushrooms.
GABA-active plant products include sesquiterpenes such as valerenic acid found in
valerian (Valeriana officinalis) or monoterpene ketones like camphene found in
Cinnamomum camphora. A more infamous plant-derived antagonist of the GABA A receptor is the monoterpene ketone thujone found in plants such as thuja, Nootka cypress,
mugwort, oregano, common sage, tansy or wormwood. Thujone has a menthol odour and
is best known as a component of Absinthe (see 7 Box 8.3), which contains extracts of the
grand wormwood, Artemisia absinthium. Thujone is considered as an addictive psychoactive drug and its use in food and drinks is therefore limited by law. In the European Union,
up to 35 mg/kg thujone is permitted for alcoholic beverages prepared from Artemisia
species with stronger limits for food and non-alcoholic beverages. Similar restrictions
8.3 · GABA A Receptors: Thujone, Cicutoxin and Anisatin