Conference Presentations by Vahe Meliksetyan
8th International Symposium on Neuroprotection and Neurorepair, 2014
8th International Symposium on Neuroprotection and Neurorepair, 2014
Current Issues of Medicinal Science Conference towards the 95th anniversary of YSMU, 2015
The influence of 5-hydroxyadamantane-2-on, an adamantane deriva-
tive, on morphological state of ... more The influence of 5-hydroxyadamantane-2-on, an adamantane deriva-
tive, on morphological state of brain tissue of rats with local permanent
brain ischemia was studied. As a model of ischemia the occlusion of left
middle cerebral artery was chosen. The comparison was done between
serial histological preparations of the control group (with occlusion
and without drug administration) and two experimental groups
(with occlusion and administration of 5-hydroxyadamantane-2-on
100 mg/kg i.p., for 6 and 12 days respectively). Moreover, within the
same histological preparations the morphological changes were
compared between histological preparations from basins of left and
right (not occluded) middle cerebral arteries.
It was determined that the administration of 5-hydroxyadamantane-
2-on (dosage 100 mg/kg) was once per day after the occlusion of
the middle cerebral artery brings to significant regenerative processes
of brain tissue. It was also shown that regenerative processes are
more profound in the group of rats that was treated with 5-
hydroxyadamantane-2-on for 12 days.
"Stroke is the most common life-threatening neurological disease, one
of the major causes of dea... more "Stroke is the most common life-threatening neurological disease, one
of the major causes of death and disability worldwide. Prevalence
of anxiety remains a common problem several years after the stroke.
5-hydroxiadamantane-2-on an adamantine derivative has cerebro-
vascular activity and improves cerebral blood flow by activating
GABA-ergic system.
The aim of this study was to reveal and evaluate anxiolytic effect of
5-hydroxiadamantane-2-on after local ischemia.
White inbred male rats were used. Anxiety was evaluated by two main
parameters of elevated plus-maze (EPM) test: percentage of entries to
open arms (OA) and time spent on OA. As a model of acute local
ischemia, the middle cerebral artery (MCA) occlusion was chosen. The
control group didn´t receive any drug, while the experimental group
has received 5-hydroxiadamantane-2-on immediately after MCA
occlusion and on the following 6 days (100 mg/kg, i.p., once daily).
In both groups the neurobehavioral changes have been tested through
EPM test a day before and on the 6th day after MCA occlusion.
The percentage of entries to OA and time spent on OA of control
group before occlusion were 27.25 ± 9.69 and 33.52 ± 3.86 and on
6th day — 19.38 ± 14.2 and 17.25 ± 11.1, relatively. For experimen-
tal group the percentage of entries to OA and time spent on OA were
12.55 ± 7.1 and 21.0 ± 5.8 before occlusion and 36.66 ± 9.12 and
69.0 ± 22.33 on the 6th day.
Thus, the results have shown that 5-hydroxiadamantane-2-on displays
anxiolytic-like effect in animals with anxiety caused by local ischemia
and can be suggested for further investigation of its anxiolytic activity."
Papers by Vahe Meliksetyan
Экспериментальная и клиническая фармакология, 2015
В опытах на крысах установлено, что курсовое 6- и 12-дневное применение мексидола или гемисукцина... more В опытах на крысах установлено, что курсовое 6- и 12-дневное применение мексидола или гемисукцината 2-этил-6-метил-3-гидроксипиридина (в дозах 200 мг/кг, внутрибрюшинно) предотвращает избыточное накопление липофусцина в ткани мозга после локальной перманентной ишемии, вызванной перевязкой средней мозговой артерии, как в интактном, так и в поврежденном полушариях головного мозга. Мексидол вызывает выраженное снижение уровня липофусцина после 12 дней введения, тогда как гемисукцинат 2-этил-6-метил-3-гидроксипиридин приводит к значительному снижению концентрации липофусцина уже после 6-дневного лечения.
Экспериментальная и клиническая фармакология, 2015
Исследовано влияние конъюгата ГАМК с арахидоновой кислотой на морфологическое состояние ткани гол... more Исследовано влияние конъюгата ГАМК с арахидоновой кислотой на морфологическое состояние ткани головного мозга крыс после перевязки левой средней мозговой артерии. Проведенное исследование позволило установить, что курсовое введение в течение 6 и 12 дней конъюгата ГАМК с арахидоновой кислотой в дозе 2 мг/кг (внутрибрюшинно) крысам, перенесшим локальную перманентную ишемию головного мозга, приводило к существенным восстановительным процессам в мозговой ткани. Морфологическая картина мозговой ткани в группе животных, получающих конъюгат ГАМК с арахидоновой кислотой в течение 12 дней, практически приближалась к показателям нормальной ткани.
Medical Science of Armenia, 2015
Բժշկություն, գիտություն և կրթություն, 2016
The anxiolytic effect of 5-hydroxyadamantane-2-on, GABA-conjugate with arachidonic acid, GABA-con... more The anxiolytic effect of 5-hydroxyadamantane-2-on, GABA-conjugate with arachidonic acid, GABA-conjugate with PgE2 and 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate was investigat¬ed on rats after the occlusion of the left middle cerebral artery. To assess behavioral changes of animals, the “elevated plus-maze” was used and the following parameters were evaluated։ time spent on open arms, time spent on center square, total number of entries and percent of open arm entries. As a control group for the treatment evaluation, intact rats were chosen, as well as those receiving normal saline solution after middle cerebral artery occlusion, for 6 and 12 days respectively.
The results have shown that all four investigated substances displayed significant improvement of behavioral outcomes after middle cerebral artery occlusion. Moreover, the mentioned effects varied qualitatively and quantitatively between the studied sub¬stances. Particularly, 2-ethyl-6-methyl-3-hydroxypyridinehemisuc¬cinate have shown significant improvement already on the 6th day of the treatment, while these results were exceeding those of the 12th day. Conversely, GABA-conjugate with arachidonic acid and GABA-conjugate with PgE2 have displayed significant im¬provement of anxiolytic-like effect while extending the treatment up to 12 days. Finally, 5-hydroxyadamantane-2-on have shown more stable improvement of behavioral tests, i. e. no significant differences have been detected between the results of the 6th and 12th days
Экспериментальная и клиническая фармакология, 2014
The influence of 2-methyl-6-ethyl-3-hydroxypyridine hemisuccinateon the morphological state of ra... more The influence of 2-methyl-6-ethyl-3-hydroxypyridine hemisuccinateon the morphological state of rat brain tissue after the occlusion of left middle cerebral artery has been studied. It was found that 6- and 12-day treatment with 2-methyl-6-ethyl-3-hydroxypyridine hemisuccinate at dose of 100mg/kg (intraperitoneal) led to regenerative processes in ischemic brain tissue. The latter treatment duration was most effective.
Экспериментальная и клиническая фармакология, 2013
The effect of 5-hydroxyadamantane-2-one was studied on morphological state of brain tissue of rat... more The effect of 5-hydroxyadamantane-2-one was studied on morphological state of brain tissue of rats after the occlusion of left middle cerebral artery. It was
shown that intraperitoneal administration of 5-hydroxyadamantane-2-on at dose 100mg/kg, in 30 minutes after occlusion and once daily for the following 6 and
12 days leads to significant regenerative processes in brain tissue. These processes were more profound after the 12-day treatment with 5-hydroxyadamanta-
ne-2-one.
Biomed Research International, Mar 20, 2014
Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow u... more Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow under the
conditions of global transient ischemia, as well as the morphological state of brain tissue under the condition of
permanent local brain ischemia and the survival rate of animals with hypergravity ischemia of the brain and the
interaction of the substance with NMDA receptors.
Methods. Study has been implemented using the method of local blood flow registration by lazer flowmeter.
We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, hypergravity
ischemia of the brain, [ 3 H]-MK-801 binding, morphological examination of the brain tissue.
Results. Unlike memantine – antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not
block NMDA receptors but enhances the cerebral blood flow of rats with global transient brain ischemia and has
no influence on intact animals. This effect is eliminated by bicuculline. Under conditions of permanent occlusion
of middle cerebral artery, 5-hydroxyadamantane-2-on in dose of 100 mg/kg administered for 6 or 12 days was
recovering compensatory regeneration in neural cells, axons, glial cells, as well as increases the number of
microcirculatory vessels. In the same dose 5-hydroxyadamantane-2-on was increasing the survival rate of animals
with hypergravity ischemia.
Conclusions. 5-hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist,
demonstrates significant cerebrovascular and neuroprotective activity in conditions of global and local brain
ischemia. This activity is manifested as improvement of blood flow of ischemic brain, prevention of structural
disturbances of the brain and increase in survival rate of hypergravity loaded rats. Presumably, the GABA-ergic
system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-
hydroxyadamantane-2-on.
Books by Vahe Meliksetyan
Training Manual for Pharmaceutical Faculty Students, 2015
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Conference Presentations by Vahe Meliksetyan
tive, on morphological state of brain tissue of rats with local permanent
brain ischemia was studied. As a model of ischemia the occlusion of left
middle cerebral artery was chosen. The comparison was done between
serial histological preparations of the control group (with occlusion
and without drug administration) and two experimental groups
(with occlusion and administration of 5-hydroxyadamantane-2-on
100 mg/kg i.p., for 6 and 12 days respectively). Moreover, within the
same histological preparations the morphological changes were
compared between histological preparations from basins of left and
right (not occluded) middle cerebral arteries.
It was determined that the administration of 5-hydroxyadamantane-
2-on (dosage 100 mg/kg) was once per day after the occlusion of
the middle cerebral artery brings to significant regenerative processes
of brain tissue. It was also shown that regenerative processes are
more profound in the group of rats that was treated with 5-
hydroxyadamantane-2-on for 12 days.
of the major causes of death and disability worldwide. Prevalence
of anxiety remains a common problem several years after the stroke.
5-hydroxiadamantane-2-on an adamantine derivative has cerebro-
vascular activity and improves cerebral blood flow by activating
GABA-ergic system.
The aim of this study was to reveal and evaluate anxiolytic effect of
5-hydroxiadamantane-2-on after local ischemia.
White inbred male rats were used. Anxiety was evaluated by two main
parameters of elevated plus-maze (EPM) test: percentage of entries to
open arms (OA) and time spent on OA. As a model of acute local
ischemia, the middle cerebral artery (MCA) occlusion was chosen. The
control group didn´t receive any drug, while the experimental group
has received 5-hydroxiadamantane-2-on immediately after MCA
occlusion and on the following 6 days (100 mg/kg, i.p., once daily).
In both groups the neurobehavioral changes have been tested through
EPM test a day before and on the 6th day after MCA occlusion.
The percentage of entries to OA and time spent on OA of control
group before occlusion were 27.25 ± 9.69 and 33.52 ± 3.86 and on
6th day — 19.38 ± 14.2 and 17.25 ± 11.1, relatively. For experimen-
tal group the percentage of entries to OA and time spent on OA were
12.55 ± 7.1 and 21.0 ± 5.8 before occlusion and 36.66 ± 9.12 and
69.0 ± 22.33 on the 6th day.
Thus, the results have shown that 5-hydroxiadamantane-2-on displays
anxiolytic-like effect in animals with anxiety caused by local ischemia
and can be suggested for further investigation of its anxiolytic activity."
Papers by Vahe Meliksetyan
The results have shown that all four investigated substances displayed significant improvement of behavioral outcomes after middle cerebral artery occlusion. Moreover, the mentioned effects varied qualitatively and quantitatively between the studied sub¬stances. Particularly, 2-ethyl-6-methyl-3-hydroxypyridinehemisuc¬cinate have shown significant improvement already on the 6th day of the treatment, while these results were exceeding those of the 12th day. Conversely, GABA-conjugate with arachidonic acid and GABA-conjugate with PgE2 have displayed significant im¬provement of anxiolytic-like effect while extending the treatment up to 12 days. Finally, 5-hydroxyadamantane-2-on have shown more stable improvement of behavioral tests, i. e. no significant differences have been detected between the results of the 6th and 12th days
shown that intraperitoneal administration of 5-hydroxyadamantane-2-on at dose 100mg/kg, in 30 minutes after occlusion and once daily for the following 6 and
12 days leads to significant regenerative processes in brain tissue. These processes were more profound after the 12-day treatment with 5-hydroxyadamanta-
ne-2-one.
conditions of global transient ischemia, as well as the morphological state of brain tissue under the condition of
permanent local brain ischemia and the survival rate of animals with hypergravity ischemia of the brain and the
interaction of the substance with NMDA receptors.
Methods. Study has been implemented using the method of local blood flow registration by lazer flowmeter.
We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, hypergravity
ischemia of the brain, [ 3 H]-MK-801 binding, morphological examination of the brain tissue.
Results. Unlike memantine – antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not
block NMDA receptors but enhances the cerebral blood flow of rats with global transient brain ischemia and has
no influence on intact animals. This effect is eliminated by bicuculline. Under conditions of permanent occlusion
of middle cerebral artery, 5-hydroxyadamantane-2-on in dose of 100 mg/kg administered for 6 or 12 days was
recovering compensatory regeneration in neural cells, axons, glial cells, as well as increases the number of
microcirculatory vessels. In the same dose 5-hydroxyadamantane-2-on was increasing the survival rate of animals
with hypergravity ischemia.
Conclusions. 5-hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist,
demonstrates significant cerebrovascular and neuroprotective activity in conditions of global and local brain
ischemia. This activity is manifested as improvement of blood flow of ischemic brain, prevention of structural
disturbances of the brain and increase in survival rate of hypergravity loaded rats. Presumably, the GABA-ergic
system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-
hydroxyadamantane-2-on.
Books by Vahe Meliksetyan
tive, on morphological state of brain tissue of rats with local permanent
brain ischemia was studied. As a model of ischemia the occlusion of left
middle cerebral artery was chosen. The comparison was done between
serial histological preparations of the control group (with occlusion
and without drug administration) and two experimental groups
(with occlusion and administration of 5-hydroxyadamantane-2-on
100 mg/kg i.p., for 6 and 12 days respectively). Moreover, within the
same histological preparations the morphological changes were
compared between histological preparations from basins of left and
right (not occluded) middle cerebral arteries.
It was determined that the administration of 5-hydroxyadamantane-
2-on (dosage 100 mg/kg) was once per day after the occlusion of
the middle cerebral artery brings to significant regenerative processes
of brain tissue. It was also shown that regenerative processes are
more profound in the group of rats that was treated with 5-
hydroxyadamantane-2-on for 12 days.
of the major causes of death and disability worldwide. Prevalence
of anxiety remains a common problem several years after the stroke.
5-hydroxiadamantane-2-on an adamantine derivative has cerebro-
vascular activity and improves cerebral blood flow by activating
GABA-ergic system.
The aim of this study was to reveal and evaluate anxiolytic effect of
5-hydroxiadamantane-2-on after local ischemia.
White inbred male rats were used. Anxiety was evaluated by two main
parameters of elevated plus-maze (EPM) test: percentage of entries to
open arms (OA) and time spent on OA. As a model of acute local
ischemia, the middle cerebral artery (MCA) occlusion was chosen. The
control group didn´t receive any drug, while the experimental group
has received 5-hydroxiadamantane-2-on immediately after MCA
occlusion and on the following 6 days (100 mg/kg, i.p., once daily).
In both groups the neurobehavioral changes have been tested through
EPM test a day before and on the 6th day after MCA occlusion.
The percentage of entries to OA and time spent on OA of control
group before occlusion were 27.25 ± 9.69 and 33.52 ± 3.86 and on
6th day — 19.38 ± 14.2 and 17.25 ± 11.1, relatively. For experimen-
tal group the percentage of entries to OA and time spent on OA were
12.55 ± 7.1 and 21.0 ± 5.8 before occlusion and 36.66 ± 9.12 and
69.0 ± 22.33 on the 6th day.
Thus, the results have shown that 5-hydroxiadamantane-2-on displays
anxiolytic-like effect in animals with anxiety caused by local ischemia
and can be suggested for further investigation of its anxiolytic activity."
The results have shown that all four investigated substances displayed significant improvement of behavioral outcomes after middle cerebral artery occlusion. Moreover, the mentioned effects varied qualitatively and quantitatively between the studied sub¬stances. Particularly, 2-ethyl-6-methyl-3-hydroxypyridinehemisuc¬cinate have shown significant improvement already on the 6th day of the treatment, while these results were exceeding those of the 12th day. Conversely, GABA-conjugate with arachidonic acid and GABA-conjugate with PgE2 have displayed significant im¬provement of anxiolytic-like effect while extending the treatment up to 12 days. Finally, 5-hydroxyadamantane-2-on have shown more stable improvement of behavioral tests, i. e. no significant differences have been detected between the results of the 6th and 12th days
shown that intraperitoneal administration of 5-hydroxyadamantane-2-on at dose 100mg/kg, in 30 minutes after occlusion and once daily for the following 6 and
12 days leads to significant regenerative processes in brain tissue. These processes were more profound after the 12-day treatment with 5-hydroxyadamanta-
ne-2-one.
conditions of global transient ischemia, as well as the morphological state of brain tissue under the condition of
permanent local brain ischemia and the survival rate of animals with hypergravity ischemia of the brain and the
interaction of the substance with NMDA receptors.
Methods. Study has been implemented using the method of local blood flow registration by lazer flowmeter.
We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, hypergravity
ischemia of the brain, [ 3 H]-MK-801 binding, morphological examination of the brain tissue.
Results. Unlike memantine – antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not
block NMDA receptors but enhances the cerebral blood flow of rats with global transient brain ischemia and has
no influence on intact animals. This effect is eliminated by bicuculline. Under conditions of permanent occlusion
of middle cerebral artery, 5-hydroxyadamantane-2-on in dose of 100 mg/kg administered for 6 or 12 days was
recovering compensatory regeneration in neural cells, axons, glial cells, as well as increases the number of
microcirculatory vessels. In the same dose 5-hydroxyadamantane-2-on was increasing the survival rate of animals
with hypergravity ischemia.
Conclusions. 5-hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist,
demonstrates significant cerebrovascular and neuroprotective activity in conditions of global and local brain
ischemia. This activity is manifested as improvement of blood flow of ischemic brain, prevention of structural
disturbances of the brain and increase in survival rate of hypergravity loaded rats. Presumably, the GABA-ergic
system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-
hydroxyadamantane-2-on.