Cerebrovascular and neuroprotective effects of adamantane derivative.
OBJECTIVE
The influence of 5-hydroxyadamantane-2-on was studied on the rats' brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied.


METHODS
Study has been implemented using the methods of local blood flow registration by laser flowmeter, [(3)H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain.


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 brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 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 brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Ruben S
RS
Mirzoyan
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Tamara S
TS
Gan'shina
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Denis V
DV
Maslennikov
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Georgy I
GI
Kovalev
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Ivan A
IA
Zimin
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Boris M
BM
Pyatin
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Nina I
NI
Avdyunina
Zakusov Institute of Pharmacology RAMS, 8 Baltiyskaya Street, Moscow 125315, Russia.
Anna M
AM
Kukhtarova
Yerevan State Medical University after Mkhitar Heratsi, 2 Koryun Street, 0025 Yerevan, Armenia.
Nelly G
NG
Khostikyan
Yerevan State Medical University after Mkhitar Heratsi, 2 Koryun Street, 0025 Yerevan, Armenia.
Vahe S
VS
Meliksetyan
Yerevan State Medical University after Mkhitar Heratsi, 2 Koryun Street, 0025 Yerevan, Armenia.
Cristina B
CB
Alikhanyan
Yerevan State Medical University after Mkhitar Heratsi, 2 Koryun Street, 0025 Yerevan, Armenia.
Narine R
NR
Mirzoyan
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D000218:Adamantane