Research and Development of a New Safe Form of Drugs - Aerosols: Measurement, Dosimetry, and Health Effects - page 272

11,63

54

38,8*

11,63

30

24,88*

11,63

49,4*

24

42*

15

11,63
11,8

6

22,39*

14,54

0 10 20 30 40 50 60

Prothrombin time (s)

WF:GA, 20 mg/kg WF, 2 mg/kg WF Nyc, 2 mg/kg Saline

FIGURE 11.19 Prothrombin time of the WF:GA (1:10). * Signiicantly different ( P < 0.05) from control

(saline).

itself only after a longer period of time and cumulation of warfarin in the organism. However, the
modern anticoagulant medicine should act faster (Aken et al., 2001) and because of this, to obtain
the desired effect we should change a complexing agent (see more in Section 11.2.1.14).

11.2.1.7 Complexes of Glycyrrhizic Acid with Psychotropic Drugs
Complexes with the following pharmacons were obtained for the examination: luoxetin (an anti-
depressant), phenibut, buspiron, diazepam, oxazepam, medazepam (anxiolytics), and azaleptin
(neuroleptic). Of these, the GA complexes with luoxetin, phenibut, and buspiron are the most well-
researched ones.
Fluoxetin (FL) ( N -methyl-3-(4′-triluoromethylphenoxy)-3-phenylpropylamin hydrochloride) is
known to cause an antidepressant action connected with inhibition of serotonin capture by neurons
in CNS. Antidepressants are known to have such disadvantages as rather high doses, a narrow range
of therapeutic index, high toxicity and long elimination period, which provide a negative effect on
kidney functions and damage hepatocytes.
The study of GA complexes with luoxetin was conducted with the main aim to determine
whether the side effects of this pharmacon could be decreased. Preliminary tests showed that the
complex with the composition GA:FL 4:1 was the most active. This complex, one weight party of
which contains 0.072 parts of pharmacon, is patented under the name Fluoglyzine (FG) (Tolstikov
et al., 2004). The complexes with the compositions 4:1 and 2:1 are characterized by LD 50 higher than
5000 mg/kg as compared with 248 mg/kg for Fluoxetin.
Fluoglyzine in the Porsolt test at a single and prolonged administration was found to have a more
pronounced antidepressant action as compared with Fluoxetine. In comparison with Fluoxetine,
Fluoglyzine produces a stronger inhibiting effect on serotonin structures. For example, in the test
with 5-oxytriptophan, luoglyzine inhibits chloral hydrate action to a greater extent than Fluoxetine.
Both drugs produce no anxiolytic effect.
In the social depression model in mice, Fluoglyzine was shown to have an antidepressant effect
similar to that of Fluoxetine, which was manifested in a twofold increase of communicability of
individuals (the number and duration of contacts) in response to a known and strange partner. The
dose of Fluoxetine in complex GA:FL 4:1 is 1.08 mg/kg as compared with 15 mg/kg for the sample
drug. Fluoglyzine, similarly to luoxetine, prevents a decrease of glucose content in blood and low-
ers the intensity of peroxidation, thereby normalizing antioxidant status of depressed individuals
(Avgustinovich et al., 2004; Kovalenko et al., 2004; Tolstikova et al., 2004).
To elucidate the action mechanism of complexes GA: FL 4:1 and 1:1 as compared with luoxetine,
their effect on the content of catecholamines and their precursors in different parts of cerebrum was
studied at a single and therapeutic administration at the dose of 25 mg/kg. A decrease of luoxetine
dose by 4 times (complex 1:1) and 17 times (complex 4:1) in complexes with GA was found to lower