102
7
suggest a quick elimination of atropine from the body of these animals, i.e. via high levels
of serum tropine esterase activity (Sawin and Glick 1943) or other types of metabolic
breakdown in the liver. Activity of the tropine esterase can vary between animals of the
same species, but pronounced activity was found in the serum of rats, chicken and rabbits
as well as the liver of frogs (Glick and Glaubach 1941). Bees supposedly can also tolerate
atropine since it has been found enriched in honey of bees pollinating deadly nightshade
plants (Hazslinszky 1956; Islam et al. 2014).
The deadly nightshade and other plants from the Solanaceae family additionally
contain the tropane alkaloids scopolamine and hyoscyamine, both of which are antagonists of muscarinic acetylcholine receptors. Scopolamine is also on the WHO Model
List of Essential Medicine and has been employed in its purified form since its first
isolation in 1880 (Ladenburg 1881); however, all of these tropane alkaloids have been
used as active ingredients of plant extracts long before. As such, these plants are well
described parts of ethnomedicine such as the use of Jimson weed and henbane in Tibet
(Ma et al. 2015).
The pyridine alkaloid arecoline is a partial agonist of the muscarinic acetylcholine receptor and as such has parasympathomimetic effects. It is found in the areca nut (Areca catechu L.) and has long been used in Chinese traditional medicine as a remedy against
tapeworm or diarrhoea (Liu et al. 2016). The nut is often chewed wrapped in betel (Piper
betle) and tobacco leaves or mixed with these and other spices thereby creating a blend of
active ingredients. It is very popular in Asia, allegedly used by about 600 million people,
making it one of the most-used plant-derived drug.
7.2 Adrenergic Receptors: Ephedrine and Reserpine
Ephedrine and the related plant-derived phenylethylamines pseudoephedrine, methylephedrine and methyl pseudoephedrine are mixed acting sympathomimetics. They
directly interact with α- and β-adrenergic receptors (. Fig. 7.3), but they also act indirectly by inhibition of the noradrenaline reuptake, thereby increasing the amount of noradrenaline in the synaptic cleft (Kobayashi et al. 2003; Reith et al. 1997). Ephedrine and
pseudoephedrine are found in plants of the Ephedra genus such as Ephedra sinica. Better
known as má huáng (麻黄), this plant has a long use in traditional Chinese medicine.
Ephedra extracts are also part of dietary supplements used to promote weight loss and
athletic performance (Shekelle et al. 2003). While on the WHO Complementary List of
Essential Medicines, there are also concerns regarding severe side effects (Haller and
Benowitz 2000; Andraws et al. 2005). The closely related phenylethylamines, norephedrine
and norpseudoephedrine, are found in Khat (Catha edulis, qat), a flowering plant whose
leaves have been chewed in its native African and Arabian range in a manner similar to the
chewing of coca leaves in South America. Very little is known about the function of these
compounds in plants. Allelopathic effects on seed germination have been observed for
Ephedra extracts, but the molecular base for these properties or its use in the natural environment is completely undetermined.
The indole alkaloid reserpine is found in the roots of Indian snakeroot (Rauvolfia serpentina), a plant widely distributed in India and the sub-Himalaya, where it has a long
history as a medicinal herb. It inhibits the “vesicular transporter for monoamine storage”
(VMAT), thereby blocking the uptake of noradrenalin (but also dopamine and serotonin)
from the cytoplasm into neuronal storage granules (Schuldiner et al. 1993). By contrast,
Chapter 7 · Plant-Derived Drugs Affecting GPRCs
7
suggest a quick elimination of atropine from the body of these animals, i.e. via high levels
of serum tropine esterase activity (Sawin and Glick 1943) or other types of metabolic
breakdown in the liver. Activity of the tropine esterase can vary between animals of the
same species, but pronounced activity was found in the serum of rats, chicken and rabbits
as well as the liver of frogs (Glick and Glaubach 1941). Bees supposedly can also tolerate
atropine since it has been found enriched in honey of bees pollinating deadly nightshade
plants (Hazslinszky 1956; Islam et al. 2014).
The deadly nightshade and other plants from the Solanaceae family additionally
contain the tropane alkaloids scopolamine and hyoscyamine, both of which are antagonists of muscarinic acetylcholine receptors. Scopolamine is also on the WHO Model
List of Essential Medicine and has been employed in its purified form since its first
isolation in 1880 (Ladenburg 1881); however, all of these tropane alkaloids have been
used as active ingredients of plant extracts long before. As such, these plants are well
described parts of ethnomedicine such as the use of Jimson weed and henbane in Tibet
(Ma et al. 2015).
The pyridine alkaloid arecoline is a partial agonist of the muscarinic acetylcholine receptor and as such has parasympathomimetic effects. It is found in the areca nut (Areca catechu L.) and has long been used in Chinese traditional medicine as a remedy against
tapeworm or diarrhoea (Liu et al. 2016). The nut is often chewed wrapped in betel (Piper
betle) and tobacco leaves or mixed with these and other spices thereby creating a blend of
active ingredients. It is very popular in Asia, allegedly used by about 600 million people,
making it one of the most-used plant-derived drug.
7.2 Adrenergic Receptors: Ephedrine and Reserpine
Ephedrine and the related plant-derived phenylethylamines pseudoephedrine, methylephedrine and methyl pseudoephedrine are mixed acting sympathomimetics. They
directly interact with α- and β-adrenergic receptors (. Fig. 7.3), but they also act indirectly by inhibition of the noradrenaline reuptake, thereby increasing the amount of noradrenaline in the synaptic cleft (Kobayashi et al. 2003; Reith et al. 1997). Ephedrine and
pseudoephedrine are found in plants of the Ephedra genus such as Ephedra sinica. Better
known as má huáng (麻黄), this plant has a long use in traditional Chinese medicine.
Ephedra extracts are also part of dietary supplements used to promote weight loss and
athletic performance (Shekelle et al. 2003). While on the WHO Complementary List of
Essential Medicines, there are also concerns regarding severe side effects (Haller and
Benowitz 2000; Andraws et al. 2005). The closely related phenylethylamines, norephedrine
and norpseudoephedrine, are found in Khat (Catha edulis, qat), a flowering plant whose
leaves have been chewed in its native African and Arabian range in a manner similar to the
chewing of coca leaves in South America. Very little is known about the function of these
compounds in plants. Allelopathic effects on seed germination have been observed for
Ephedra extracts, but the molecular base for these properties or its use in the natural environment is completely undetermined.
The indole alkaloid reserpine is found in the roots of Indian snakeroot (Rauvolfia serpentina), a plant widely distributed in India and the sub-Himalaya, where it has a long
history as a medicinal herb. It inhibits the “vesicular transporter for monoamine storage”
(VMAT), thereby blocking the uptake of noradrenalin (but also dopamine and serotonin)
from the cytoplasm into neuronal storage granules (Schuldiner et al. 1993). By contrast,
Chapter 7 · Plant-Derived Drugs Affecting GPRCs