Biomedical Engineering Reference
In-Depth Information
Most TA referred herein (e.g. hyoscyamine, scopolamine,
N
-butyl-scopolamine,
Fig.
1
) primarily act as competitive antagonists of acetylcholine (anticholinergics)
in the synaptic cleft (parasympatholytic) [
29,
35
]. Thus therapeutic effects may
include mydriasis, spasmolysis of the respiratory system, GIT and overactive blad-
der, anaesthesia and analgesia [
33
] .
Nevertheless, certain TA are known to exhibit agonistic activity (cholinergics),
e.g. (−)-satropane (Fig.
1
) or baogongteng [
4
]. These compounds cause, e.g. smooth
muscle contraction and may exhibit protective and trophic effects on retinal gan-
glion cells thus being considered for the treatment of glaucoma [
4
] .
2.2.4
Binding to 5-HT
3
R
The 5-HT
3
R receptor is expressed in areas involved in the emetic reflex in the CNS
and GIT. Serotonin (5-hydroxytryptamine) functions as its physiological agonist
mediating neuronal excitations involving a ligand-gated cation channel [
36
] . Due to
chemotherapy, serotonin release is increased thus causing vomiting and nausea.
Regulation by antagonization is recommended for therapy.
Some synthetic TA primarily act as selective serotonin antagonist and are thus
considered and used as antiemetics, including bemesetron, granisetron, tropisetron
and scopolamine (Fig.
1
) [
36,
37
] .
2.2.5
Binding to a 1-AR and a 7-nAChR
a1-AR plays an important role in blood pressure regulation as well as contraction
and growth of smooth and cardiac muscles. Anisodamine and anisodine (Fig.
1
) are
muscarinic cholinergic antagonists and they also exhibit blocking activity on a 1-AR.
This mechanism supports the clinical use to treat septic shock by improvement of
blood flow (vasodilation of the microcirculation) [
38
] .
Tropisetron (a selective 5-HT
3
R antagonist, Fig.
1
) has been found to be also a
potent and selective but partial agonist of a7-nAChR thus potentially effecting learning
and memory processes [
39
]. Clinical implications and use are still not elaborated.
2.2.6
TA Analysed by LC-MS Methods
In the following, 19 individual TA are listed in alphabetical order that represent
analytes of referred LC-MS procedures. The short summaries provide important
keywords for characterizing important background information.
Anisodamine
(Ada; C
17
H
23
NO
4
; MW 305.16 g/mol; CAS-No; 55869-99-3;
[(1S,3S,5S,7S)-7-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-3-yl] (2S)-3-hydroxy-
2-phenyl-propanoate).
Anisodamine is a natural derivative of hyoscyamine mono-hydroxylated at the
tropane skeleton (Fig.
1
). The compound was extracted from traditional Chinese
medicine
Anisodus tanguticus
evoking typical non-specific effects of cholinergic
antagonists (spasmolysis, anaesthesia, mydriasis, analgesia) in combination with
