Mendeleev Commun., 2018, 28, 317–319
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Control
Ketanserin
Ketanserin + racemate
Ketanserin + EN1
Ketanserin + EN2
(a)
60
50
40
30
20
10
0
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30 min
60 min
Control
Ketanserin
Ketanserin + racemate
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Ketanserin + EN2
(b)
20
15
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5
*
*
*
*
*
*
0
30 min
60 min
Figure 3 Changes in the results of the ‘open field’ test after administering
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pharmacological characteristics of animals blocks the stimulating
properties of enantiomer 1 by the 30th minute and enhances the
inhibitory properties of both enantiomers and Albicar racemate
throughout the entire experiment (Figure 3).
In the tests with 5-hydroxytryptophan, Albicar racemate and
enantiomer 2 did not reliably change the intensity of hyperkinesis
caused by 5-hydroxytryptophan. However, enantiomer 1 reliably
potentiated the action of the dose of 300 mg kg–1 5-hydroxy-
tryptophan: the number of head shakings increased to 50.00±5.33
in comparison with 27.80±2.40 in the reference group of animals
(Figure S3).
In conclusion, we have performed a two-stage synthesis of Albicar
racemate. To obtain enantiomers 1 and 2 in 50 mg amounts, a
chiral HPLC method for racemate separation has been used
for the first time. An in vivo study of Albicar racemate showed
the effective dose to be 150 mg kg–1, which was then used in
the comparative analysis of the effects of Albicar racemate and
enantiomers (the dose of the latter was half that, i.e., 75 mg kg–1).
The lack of an effect of Albicar racemate on the motional and
exploratory activity by the 30th minute of the experiment was
found to be due to the competing mutually exclusive effects
of the two enantiomers (enantiomer 1 has a stimulating effect
on the CNS while enantiomer 2 has an inhibitive effect), whereas
both enantiomers act in an inhibitive way at the 60th minute.
Comparison of the behavioural reactions of mice after administering
racemic Albicar and enantiomers with background action of
Yohimbine and Ketanserin has shown that the action of enantio-
mer 1 is most likely due to the activation of the serotoninergic
system, since it potentiates the effects of 5-hydroxytryptophan,
a serotonin precursor, while the antagonist of serotonin receptors
blocks its activity. The mechanism of action of enantiomer 2
requires further studies.
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This study was supported by the Russian Science Foundation
(grant no. 17-73-10415).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2018.05.030.
Received: 11th December 2017; Com. 17/5430
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