Volume 02 Issue 09-2022
1
International Journal of Medical Sciences And Clinical Research
(ISSN
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2771-2265)
VOLUME
02
I
SSUE
09
Pages:
01-05
SJIF
I
MPACT
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(2021:
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694
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(2022:
5.
893
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OCLC
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1121105677
METADATA
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5.654
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Research Article
STUDY OF PSYCHOACTIVE ACTIVITY POTASSIUM SALT 5-(O-
AMINOPHENYL)-1,3,4- OXADIAZOLE-2-THION (D-361)
Submission Date:
September 05, 2022,
Accepted Date:
September 15, 2022,
Published Date:
September 24, 2022
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume02Issue09-01
S.Z. Rashidov
Junior scientific Researcher at the S.Y. Yunusov Institute of Plant Chemistry of the Academy of Sciences of the
Republic of Uzbekistan
S.D. Rakhimboev
Basic doctoral student of the Institute of Plant Chemistry named after S.Yu. Yunusov of the Academy of
Sciences of the Republic of Uzbekistan
Z.I. Sanoev
PhD, Senior scientific Researcher at the S.Yu. Yunusov Institute of Plant Chemistry of the Academy of Sciences
of the Republic of Uzbekistan
I.T. Abdinazarov
Basic doctoral student of the Institute of Plant Chemistry named after S.Yu. Yunusov of the Academy of
Sciences of the Republic of Uzbekistan
T.T. Khamroev
Basic doctoral student of the Institute of Plant Chemistry named after S.Yu. Yunusov of the Academy of
Sciences of the Republic of Uzbekistan
D.S. Ismailova
PhD, Senior scientific Researcher at the S.Yu. Yunusov Institute of Plant Chemistry of the Academy of Sciences
of the Republic of Uzbekistan
B.J.Elmuradov
Ds Doctor of Chemical Sciences, professor at the S.Yu. Yunusov Institute of Plant Chemistry of the Academy of
Sciences of the Republic of Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 02 Issue 09-2022
2
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
02
I
SSUE
09
Pages:
01-05
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
OCLC
–
1121105677
METADATA
IF
–
5.654
Publisher:
Oscar Publishing Services
Servi
ABSTRACT
These papers present a study of the synthetic compound potassium salt 5-(o-aminophenyl)-1,3,4-oxadiazol-2-thione
(D-361) at doses of 10; 30 and 60 mg/kg by oral administration on motor activity, locomotor action of phenamine,
haloperidol catalepsy and M-cholinergic receptors in experimental animals. Based on the results of the experiment, it
was found that psychostimulating, partially dopamine-blocking, M-cholinergic blocking action.
KEYWORDS
Potassium salt 5-(o-aminophenyl)-1,3,4-oxadiazol-2-thione, haloperidol, psychostimulant, phenamine.
INTRODUCTION
Psychotropic drugs are psychoactive substances used
to influence the chemical composition of components
of the brain and nervous system. In most cases, they
are created from synthetic chemical compounds. They
are usually used for the treatment of mental disorders
and are often prescribed by attending physicians in
psychiatric medical institutions during involuntary
hospitalization. In the middle of the XX century, such
drugs became the leading methods of treating a wide
range of mental illnesses: because of this, the need for
long-term hospitalization decreased, which lowered
the cost of psychiatric care [1-3]. However, in many
countries, the rate of relapses or re-hospitalization of
mentally ill patients remains high, and the reasons for
this are under investigation [4-6]. In the department of
organic synthesis, a new chemical compound has been
synthesized, which has psychotropic activity.
Purpose of the study
: To study the psychotropic
activity of 5 potassium salt 5-(o-Aminophenyl)-1,3,4-
oxadiazole-2-thion (D-361).
MATERIALS AND METHODS
The effect of substances on the motor activity of white
mice with a single injection. The experiments were
conducted on white mice where motor activity (further
MA) was estimated by the number of intersections of
the floor lines by mice in 1 min. Psychopharmacological
effects of phenamine are caused mainly by stimulation
of central α-adrenergic receptors according to
R.Rothman at al., 2001 [7]. The effect of substances on
the severity of the locomotor action of phenamine was
studied. An increase in the severity of the locomotor
action of phenamine against the background of the
administration of the studied substances compared
with control mice was assessed as an increase in the
sensitivity of central α-adrenergic receptors, and a
weakening of the locomotor action was assessed as
their blockade. The effect of substances on haloperidol
catalepsy [8]. As is known, neuroleptics, including the
D-blocker haloperidol, cause catalepsy, mainly due to
the blockade of D-receptors. The blockade of D-
receptors manifests itself in the form of immobilization
of mice and the ability to maintain an unusual pose - the
Volume 02 Issue 09-2022
3
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
02
I
SSUE
09
Pages:
01-05
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
OCLC
–
1121105677
METADATA
IF
–
5.654
Publisher:
Oscar Publishing Services
Servi
"lecturer's pose", expressed in standing on the hind
legs, and the front paws on the crossbar. The average
duration of standing on the hind legs in seconds was
recorded for the group. Shortening the catalepsy time
was evaluated as a D-positive effect, and lengthening
as a D-blocking effect. Haloperidol was administered at
a dose of 0.25 mg/kg s/c, causing catalepsy from 60 to
120 seconds. The study of the effect of substances on
M-cholinergic receptors was carried out on white mice
with the introduction of arecoline 10.0 mg/kg s/c.
Description of the method in Khabriev's manual [9].
Statistical processing of the results was carried out by
the tabular method proposed by R.B. Strelkov [10].
RESULTS AND CONCLUSIONS
The effect of substances D-361 on the motor activity of
white mice with a single injection. Doses of 10, 30 and
60 mg/kg orally were used for study MA substances. In
mice, against the background of D-361 administration
at doses of 10 and 30 mg/ kg, it was 30-45% higher than
in control mice. At a dose of 60 mg/kg with a 5-hour
follow-up, MA decreased to 35% (see. tab-1).
Table-1. The effect of substances D-361 on the motor activity of white mice with a single injection.
№
Substances
Source
1 hour
3 hour
5 hour
1.
Control
15,6±4,2
(100%)
14,8±2,3
(95%)
12,4±1,7
(79%)
9,6±1,1
(61%)
2.
D-361 10 mg/kg р.о.
12,4±2,7
(100%)
17,4±2,6*
(140%)
18,0±2,3*
(145%)
17,6±2,1*
(141%)
3.
D-361 30 mg/kg р.о.
15,8±2,1
(100%)
18,6±3,2*
(118%)
20,8±2,6*
(133%)
17,1±0,4*
(108%)
4.
D-361 60 mg/kg р.о.
16,4±3,2
(100%)
14,8±4,1*
(90%)
12,1±2,1*
(74%)
10,5±0,2*
(64%)
Note.*P≤0.05 comparison with the control group
Motor activity in white mice was monitored for several
hours by oral administration of 10-60 mg/kg. Compared
with the control group, the activity of D-361 at a dose
of 10-30 mg/kg is 30-45% higher than in control mice. At
a dose of 60 mg/kg, the activity decreased compared
to the control group.
The effect of D-361 substances on motor activity
against the background of phenamine hyperreactivity
in white mice with a single injection.
In experiments on mice, D-361 was administered in
doses of 10, 30 and 60 mg/kg orally and after 1 hour
phenamine 7.0 mg/kg s/c was administered. As
experiments showed, 5 hours after administration of
phenamine, there was an increase in motor activity in
both control mice and experimental mice, and against
the background of 10 mg/kg doses of D-361,
respectively, from 21 to 143% (p < 0.05), and from a dose
of 30 and 60 mg/kg, respectively, 61 and 15% (p≤0.05),
in all experiments there was a clear tendency to
increase motor activity compared to the control group
(see. tab-2).
Volume 02 Issue 09-2022
4
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
02
I
SSUE
09
Pages:
01-05
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
OCLC
–
1121105677
METADATA
IF
–
5.654
Publisher:
Oscar Publishing Services
Servi
Table-2. The effect of substances D-361 on the motor activity of white mice with a single injection.
№
Substances
Source
1 hour
Phenamine
1 hour
Phenamine
2 hour
Phenamine
3 hour
Phenamine
4 hour
1.
Control
(phenamine 7
mg/kg s.c.)
12,0±1,9
(100%)
14,2±2,9
(118%)
14,7±3,8
(122%)
17,2±4,7
(143%)
16,6±4,1
(138%)
14,7±3,9
(122%)
2.
D-361 10
mg/kg р.о.
12,4±2,2
(100%)
16,4±2,7
(132%)
21,8±3,8*
(175%)
30,2±4,1*
(243%)
28,6±3,9*
(230%)
20,6±2,6*
(166%)
3.
D-361 30
mg/kg р.о.
20,8±2,1
(100%)
22,4±2,4
(107%)
30,2±4,7*
(145%)
33,6±2,6*
(161%)
31,2±0,4*
(150%)
24,7±0,4*
(118%)
4.
D-361 60
mg/kg р.о.
17,8±2,7
(100%)
15,4±3,4
(86,5%)
20,5±2,6*
(115%)
19,6±2,3*
(110%)
10,4±2,1*
(58,4%)
10,4±2,1*
(58,4%)
Note.*P≤0.05 comparison with the control group
Based on the results obtained, it can be concluded
about the real potentiation of small doses of D-361 of
the locomotor action of phenamine.
The effect of substances D-361 on haloperidol
catalepsy. In the experiments conducted on mice, D-
361 was administered in doses of 10, 30 and 60 mg / kg
orally 1 hour before the administration of haloperidol
0.5 mg/kg s/c. The study showed that haloperidol itself
caused catalepsy lasting more than 140 seconds for 5
hours, while against the background of D-361, the
duration of catalepsy was less pronounced by 10-15%. It
can be concluded that the compound in doses of 10 and
30 mg/kg partially blocks the action of haloperidol.
The effect of D-361 on the resorptive effect of
arecoline. When studying the mechanism of action of
psychotropic substances on the central nervous
system, identifying the features of their effect on
central and peripheral M-cholinergic receptors is
mandatory. Experiments on the effect of M-cholinergic
receptors were carried out on 36 white male mice.
Arecoline was administered at a dose of 10.0 mg/kg,
causing salivation (peripheral effect) and tremor
(central effect). Attention was paid to the duration of
salivation and tremor. D-361 in all studied doses 10; 30
and 60 mg/kg reduces both the central and peripheral
M-cholinopositive effects of arecoline.
CONCLUSIONS
Synthetic compound 5 potassium salt 5-(o-
Aminophenyl)-1,3,4- oxadiazole-2-thion (D-361) has a
Volume 02 Issue 09-2022
5
International Journal of Medical Sciences And Clinical Research
(ISSN
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2771-2265)
VOLUME
02
I
SSUE
09
Pages:
01-05
SJIF
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MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
OCLC
–
1121105677
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Publisher:
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psychostimulating, partially dopamine-blocking, M-
choline-blocking effect.
REFERENCES
1.
Gerald N. Grob.
Chapter 3 Mental health policy in
modern America (англ.) // Oxford Textbook of
Community Mental Health / Graham Thornicroft,
George Szmukler, Kim T Mueser, Robert E.
Drake. — Oxford University Press, 2010-01-
01. doi:10.1093/med/9780199565498.003.0014.
2.
Thomas Becker, Markus Koesters.
Psychiatric outpatient clinics (англ.) // Oxford
Textbook of Community Mental Health / Graham
Thornicroft, George Szmukler, Kim T Mueser,
Robert E. Drake. — Oxford University Press, 2010-
01-
01. doi:10.1093/med/9780199565498.003.0086.
3.
Jonathan Shaywitz, Stephen Marder.
Medication treatment for anxiety, depression,
schizophrenia, and bipolar disorder in the
community setting (англ.) // Oxford Textbook of
Community Mental Health / Graham Thornicroft,
George Szmukler, Kim T Mueser, Robert E.
Drake. — Oxford University Press, 2010-01-
01. doi:10.1093/med/9780199565498.003.0109.
4.
Luis Eduardo Jaramillo-Gonzalez, Ricardo Sanchez-
Pedraza, Maria Isabel Herazo.
rehospitalization and associated factors in
Colombian
psychiatric patients: a cohort
study (англ.) // BMC Psychiatry. — 2014-12. — Vol.
14, iss. 1. — P. 161. doi:10.1186/1471-244X-14-161.
5.
Igor Oyffe, Rena Kurs, Marc Gelkopf, Yuval
Melamed, Avi Bleich.
Public Psychiatric Hospital in Israel: Cross
Sectional Study // Croatian Medical Journal. —
2009-12. — Т. 50, вып. 6. — С. 575–
582. doi:10.3325/cmj.2009.50.575.
6.
Ulrich Frick, Hannah Frick, Berthold Langguth,
Michael
Landgrebe,
Bettina
Hübner-
Liebermann.
Revisited: Time to Readmission in 17’415 Patients
with 37’697 Hospitalisations at a German
Psychiatric Hospital (англ.) // PLoS ONE / James D.
Clelland. — 2013-10-08. — Vol. 8, iss. 10. — P.
e75612. doi:10.1371/journal.pone.0075612.
7.
Rothman R., Baumann M. , Dersch C. et al. /
Amphetamine-type central nervous system
stimulants release norepinephrine more potently
than they release dopamine and serotonin. //
Synapse. 2001 Jan;39(1):32-41.
8.
Reavill C., Kettle A., Holland V., Riley G.,Blackburn
T.P. / Attenuation of haloperidol-induced
catalepsy by a 5-HT
2C
receptor antagonist.// Br. J.
Pharmacol. Feb 1999; 126(3): 572-574. ID. PMC
1565856
9.
Хабриев
Р.У.(Ред.).
Руководство
по
экспериментальному
(доклиническому)
изучению новых фармакологических веществ.
Москва. 2005, с.832.
10.
Стрелков Р.Б. Статистические таблице для
ускоренной
количественной
оценки
фармакологического эффекта. Фармакология и
токсикология 1986. №4 с.100-104.
