131
8
Strychnine is found in the bark and the seeds of Strychnos plants. Very little is known
on the natural function of strychnine for the plant; however, several possibilities can be
deduced from its properties. Strychnine has a very bitter taste, making it a good feeding
deterrent. Indeed, it was shown that larvae of the butterfly Pieris rapae responded negatively to strychnine in feeding experiments (Zhou et al. 2009). Moreover, the quick onset
of negative effects on the central nervous system caused by strychnine could efficiently
protect plants from herbivory.
Despite its toxic properties, strychnine was used early on as a performance enhancement drug (see 7 Box 8.4). In 1917, Lashley reported on a scientific study showing that
rats injected with strychnine navigated mazes faster and with a reduced error rate (Lashley
1917). However, it should be noted that already a few years later, these results were put
into question (Miles 1929). A number of subsequent studies have provided varying
results, many of them supporting a learning enhancement effect of strychnine (McGaugh
and Roozendaal 2009). Long before these experiments, the general population had discovered strychnine as a pick-me-up and would take it as a stronger version of coffee. Even
today, strychnine is used as an athletic performance enhancer (the bronze medallist in
weightlifting of the 2016 Olympics lost his medal for strychnine doping), and it is therefore on the prohibited list of the World Anti-Doping Agency.
Another, much less famous plant-derived secondary metabolite targeting the glycine
receptor is tutin, a sesquiterpenoid and one of the two main toxic compounds found in
species of the Coriaria genus, such as the New Zealand Tutu plant (Fuentealba et al. 2007).
While Coriaria extracts are being used in Chinese traditional medicine to treat mental
diseases, it might also lead to seizures.
Tutin has similar properties as strychnine and most likely the same function for the
plant; however, only little research has been done on the Coriaria toxins compared to
strychnine. Similar to atropine it has been found in honey of bees feeding honeydew exudate from the sap-sucking passion vine hopper and is therefore often described as a honey
toxin (Islam et al. 2014).
8.5 Ionotropic Glutamate Receptors: Ibogaine, Kainic
and Domoic Acid
Ibogaine is a terpenoid indole alkaloid that acts as an antagonist on the NMDA type of
ionotropic glutamate receptors (Popik et al. 1995) (. Fig. 8.6). However, it should be noted
that affinity for a number of other receptors, i.e. κ-opoid, 5HT and nicotine acetylcholine
Box 8.4 Strychnine and the 1904 Olympics
The use of strychnine as a performance enhancement drug became famous due to the 1904
Olympic marathon. Taking place in very hot weather and without the drinking stations that are
common today, the race took its toll on the 32 participants. The winner, Thomas Hicks, received
several injections of strychnine during the race (together with a great amount of brandy), and
albeit being able to finish, he was severely dehydrated and weak. While his trainer believed that
the strychnine was responsible for the victory, nowadays scientists are much more doubtful. On a
side note, Thomas Higgins had initially come in second, but the erstwhile winner of the race,
Frederick Lorz, was later disqualified for cheating, since he had driven part of the race by car
8.5 · Ionotropic Glutamate Receptors: Ibogaine, Kainic and Domoic Acid
8
Strychnine is found in the bark and the seeds of Strychnos plants. Very little is known
on the natural function of strychnine for the plant; however, several possibilities can be
deduced from its properties. Strychnine has a very bitter taste, making it a good feeding
deterrent. Indeed, it was shown that larvae of the butterfly Pieris rapae responded negatively to strychnine in feeding experiments (Zhou et al. 2009). Moreover, the quick onset
of negative effects on the central nervous system caused by strychnine could efficiently
protect plants from herbivory.
Despite its toxic properties, strychnine was used early on as a performance enhancement drug (see 7 Box 8.4). In 1917, Lashley reported on a scientific study showing that
rats injected with strychnine navigated mazes faster and with a reduced error rate (Lashley
1917). However, it should be noted that already a few years later, these results were put
into question (Miles 1929). A number of subsequent studies have provided varying
results, many of them supporting a learning enhancement effect of strychnine (McGaugh
and Roozendaal 2009). Long before these experiments, the general population had discovered strychnine as a pick-me-up and would take it as a stronger version of coffee. Even
today, strychnine is used as an athletic performance enhancer (the bronze medallist in
weightlifting of the 2016 Olympics lost his medal for strychnine doping), and it is therefore on the prohibited list of the World Anti-Doping Agency.
Another, much less famous plant-derived secondary metabolite targeting the glycine
receptor is tutin, a sesquiterpenoid and one of the two main toxic compounds found in
species of the Coriaria genus, such as the New Zealand Tutu plant (Fuentealba et al. 2007).
While Coriaria extracts are being used in Chinese traditional medicine to treat mental
diseases, it might also lead to seizures.
Tutin has similar properties as strychnine and most likely the same function for the
plant; however, only little research has been done on the Coriaria toxins compared to
strychnine. Similar to atropine it has been found in honey of bees feeding honeydew exudate from the sap-sucking passion vine hopper and is therefore often described as a honey
toxin (Islam et al. 2014).
8.5 Ionotropic Glutamate Receptors: Ibogaine, Kainic
and Domoic Acid
Ibogaine is a terpenoid indole alkaloid that acts as an antagonist on the NMDA type of
ionotropic glutamate receptors (Popik et al. 1995) (. Fig. 8.6). However, it should be noted
that affinity for a number of other receptors, i.e. κ-opoid, 5HT and nicotine acetylcholine
Box 8.4 Strychnine and the 1904 Olympics
The use of strychnine as a performance enhancement drug became famous due to the 1904
Olympic marathon. Taking place in very hot weather and without the drinking stations that are
common today, the race took its toll on the 32 participants. The winner, Thomas Hicks, received
several injections of strychnine during the race (together with a great amount of brandy), and
albeit being able to finish, he was severely dehydrated and weak. While his trainer believed that
the strychnine was responsible for the victory, nowadays scientists are much more doubtful. On a
side note, Thomas Higgins had initially come in second, but the erstwhile winner of the race,
Frederick Lorz, was later disqualified for cheating, since he had driven part of the race by car
8.5 · Ionotropic Glutamate Receptors: Ibogaine, Kainic and Domoic Acid