Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin.

We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBA×C57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an α1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound.

[PECULIARITIES OF THE CEREBROVASCULAR EFFECTS OF GLUTAMIC ACID].

Experiments on nonlinear rats subjected to global transient cerebral ischemia revealed the ability of glutamic acid to improve cerebral circulation. Consequently, the excitatory amino acid can produce adverse (neurotoxic) and positive (anti-ischemic) effects in cerebral ischemia. The cerebrovascular effect of glutamic acid in cerebral ischemia is attenuated on the background action of the MNDA receptor blocker MK-801 (0.

[ANTIPLATELET AND ANTI-ISCHEMIC EFFECTS OF MEMANTINE AND 5-HYDROXYADAMANTAN-2-ONE IN PATIENTS WITH CEREBROVASCULAR PATHOLOGY AND IN EXPERIMENTS].

It was investigated the effect of two adamantane derivatives, memantine and 5-hydroxyadamantan-2-one (5-HA), in patients with cerebrovascular disorders. In vitro studies showed that 5-HA, unlike memantine, exhibited antiplatelet activity. Experiments showed that memantine reduced cerebral blood flow in the brain cortex of intact rats and those under conditions of transient global ischemia, whereas 5-HA only selectively improved blood flow in ischemic brain and was superior to the reference drug nimodipine.

[NEUROCHEMICAL STUDY OF TROPOXIN EFFECTS ON THE CONTENT OF MONOAMINES AND ITS METABOLITES IN WISTAR RAT BRAIN STRUCTURES].

The influence of perspective anti-migraine drug tropoxin on the content of monoamines and related metabolites in Wistar rat brain structures, including frontal cortex (FC), hypothalamus, nucleus accumbens (NA), striatum, and hippocampus, has been studied using HPLC/ED technique. Tropoxin (10 mg/kg) induced a 30% decrease (p < 0.05) in dopamine (DA) level in FC as well as norepinephrine content in NA, while the concentrations of DA metabolites DOPAC and HVA in the hypothalamus were found to increase.

[ANTIARRHYTHMIC EFFECTS OF 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE HEMISUCCINATE IN COMPARISON TO MEXIDOL.].

Based on the results of experiments on nonlinear white awake male rats it is established that 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate and mexidol exhibit a pronounced antiarrhythmic (antifibrillatory) activity on the calcium chloride arrhythmia model. The maximum effect was observed for hemisuccinate 2-ethyl-6-methyl-3-hydroxypyridine. This substaned; unlike mexidol, also showed high activity on the model of aconitine arrhythmia, which is typical of class I antiarrhytmics.

[GABA-ergic mechanism of cerebrovascular and antiischemic effects of docosahexaenoic acid].

In experiments on rats, measurements of the local blood flow in the cortex of cerebrum with the aid of a laser Doppler flow meter showed that docosahexaenoic acid (DHA) enhanced the local cerebral circulation in animals with global transient cerebral ischemia, while not influencing that in intact animals. This vasodilatory effect of DHA in ischemized rats is blocked by bicuculline (specific GABA(A) receptor blocker), which is indicative of a GABA-ergic mechanisms of the vascular tone regulation. The results of radioligand binding assay in vitro showed the possibility of direct DHA interaction with cerebrovascular GABA(A) receptors.

[Effect of S-amlodipine nicotinate on the cerebral circulation in rats under conditions of ischemic and hemorrhagic brain injury].

We have performed a comparative study of the effects of S-amlodipine nicotinate and nimodipine on the local cerebral blood flow were studied in intact rats and those with model ischemic and hemorrhagic brain injury. It is established that S-amlodipine nicotinate produces a somewhat more pronounced enhancement of cerebral blood flow in rats with ischemic and hemorrhagic brain injury than in intact animals. In addition, S-amlodipine nicotinate significantly exceed nimodipine with respect to cerebrovascular activity in rats with brain pathology of both ischemic and hemorrhagic nature.

[Comparative study of the effect of S-amlodipine nicotinate and amlodipine benzylate on the arterial pressure of awake rats].

We have performed a comparative study of the effects of two calcium channel blockers, S-amlodipine nicotinate and amnlodipine benzylate, on the arterial pressure (AP) of awake rats measured in the tail artery. The results of experiments showed that both preparations produce a statistically significant long-term decrease in the AP of animals. In respect of both strength and duration of the hypotensive effect, S-amlodipine nicotinate somewhat exceeds amnlodipine benzylate.

[GABAergic mechanism of cerebrovascular effect of the NMDA receptor antagonist MK-801].

NMDA receptor antagonist MK-801 (dizocilpine) increases the local blood flow in the cerebral cortex in rats under transient global ischemia (TGI) conditions to a greater degree than in intact animals. The GABA receptor blocker bicuculline in most experiments eliminates or reduces the MK-801 induced increase in the blood flow after TGI, which is indicative of the participation of GABAergic mechanism of cerebrovascular tone control in the observed MK-801 activity.

[Cerebrovascular pharmacology of separate and combined vascular pathology of brain and heart].

The effect of nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA conjugates with arachidonic acid and docosahexaenoyl dopamine on the cerebral circulation has been studied in intact rats and those with global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. The most pronounced vasodilation activity in rats with global transient cerebral ischemia is exhibited by nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA-containing lipid derivatives. This effect of all these drugs (except for nimodipine) is not manifested on the background of GABA receptor blocker bicuculline.

Cerebrovascular and neuroprotective effects of adamantane derivative.

Objectives: 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.

[Search for new drugs with antiarrhythmic properties among derivatives of adamant-2-ylamides of alkylamidocarbonic acids].

The experiments on white outbred awaken male rats have shown that derivatives of adamant-2-ylamides of alkylamidocarbonic acids exhibit prominent antiarrhythmic (antifibrillatory) effect on the model of calcium chloride arrhythmia. The most pronounced effect was demonstrated by N-[2(adamant-2-yl)aminocarbonylmethyl]-N'-[3-(diethylamino)propyl]-4-nitrobenzamide. This compound was also active on the model of aconitine arrhythmia, which is characteristic of class-I antiarrhythmic agents.

[Cerebrovascular effects of GABA-prostaglandin E2 conjugate in comparison with prostaglandin E2].

Experiments have shown that GABA conjugate with prostaglandin E2 enhances cerebral blood flow in rats after global transient ischemia, while not affecting the cerebral hemoperfusion in intact animals. It is established that cerebrovascular activity of the GABA conjugate with prostaglandin E2 under conditions of cerebral ischemia is based on GABAergic mechanisms of vascular tone regulation, since it is removed by GABA(A)-receptor blocker bicuculline. At the same time, cerebral blood flow of intact rats and rats after global transient ischemia of brain is equally enhanced by prostaglandin E2 alone.

[Peculiarities of cerebrovascular effects of GABA conjugate with docosahexaenoyl dopamine under conditions of separate and combined vascular pathology of brain and heart].

A GABA conjugate with docosahexaenoyl dophamine (DHED) enhanced local cerebral blood flow in rats under conditions of global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. At the same time, the GABA-DHED conjugate did not influence brain hemoperfusion in intact animals. The cerebrovascular effect of this conjugate is determined by its direct action on the vascular tone, since no changes in blood pressure have been observed.

[Adamantane derivate enhances cerebral blood flow under conditions of ischemic brain damage].

Experiments have shown that adamantane derivate - 5-hydroxyadamantan-2-on (100 mg/kg, i.v.) enhances the local blood flow in the cerebral cortex of rats under global transient brain ischemia conditions, while not influencing the brain blood flow in intact rats.

[GABAergic mechanism of the cerebrovascular effect of melatonin].

In most experiments on rats under conditions of cerebral global transient ischemia, melatonin substantially enhanced local blood flow and decreased arterial blood pressure. In intact rats, the effect of melatonin on brain perfusion was much less pronounced and the arterial pressure was not influenced at all. The mechanism of melatonin action has been studied with the aid of bicuculline.

[Cerebrovascular effects of GABA conjugate with arachidonic acid under conditions of separate and combined vascular pathology of brain and heart].

Experiments on rats showed that, under conditions of global transient ischemia, a conjugate of GABA with arachidonic acid enhances the local cerebral blood flow due to a decrease in the vascular tone. In intact rats, the examined neurolipin did not show unidirectional changes in the cerebral perfusion. Under conditions of experimental myocardial infarction and combined vascular pathology of brain and heart, the GABA conjugate with arachidonic acid increased the blood flow in the parietal region of brain cortex in most experiments, while decreasing the level of blood pressure.

[Cerebrovascular and antiserotoninergic activity of the combination of tropoxin and mexidol].

The results of experiments on narcotized rats showed that tropoxin substantially reduces the constrictor reactions of cerebral blood vessels to meta-chlorophenylpiperazine, while not increasing the blood flow in the carotid system of either intact rats or animals with model ischemic damage of brain. In contrast, mexidol increases the cerebral blood flow in rats under conditions of global transient ischemia of brain. A combination of tropoxin and mexidol retains both the anti-serotoninergic activity of tropoxin and the vasodilating effect of mexidol.

[Influence of 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate on cerebral blood perfusion in rats under experimental pathology conditions].

Experiments on rats showed that 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate increases cerebral blood flow in the system of carotid arteries both in intact animals and under conditions of global transient ischemia. In combination with tropoxin, 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate enhances the blood flow in the inner carotid artery of intact rats and the local blood flow under conditions of global transient ischemia. A combination of 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate and tropoxin increases baseline cerebral blood flow and decreases the constrictor reaction of cerebral blood vessels to 5HT(2B/2C) receptor agonist meta-chlorophenylpiperazine.

[Effect of mexidol on combined vascular pathology of brain and heart].

The effect of mexidol on cerebral blood flow under conditions of experimental myocardial infarction and combined disturbances of cerebral and coronary perfusion in comparison with intact and false-operated rats and rats after global transient ischemia of brain was studied. It is established that mexidol (200 mg/kg) more prominently enhances the blood flow in the parietal region of brain cortex of rats with combined ischemia of brain and heart as compared to intact rats and rats after experimental myocardial infarction. Under conditions of combined pathology, mexidol produces the same cerebrovascular effect as that in animals with cerebral ischemia.

[GABAergic mechanism of cerebrovasculareffect of mexidol].

Experiments on rats showed that mexidol significantly increases local cerebral blood flow in animals under conditions of global transient brain ischemia, whereas in intact rats this drug initially causes a decrease in the blood flow, followed by its recovery. Mechanism of the cerebrovascular effect of mexidol is determined by its action on GABA receptors of cerebral vessels, which confirmed the fact that the cerebrovascular effect of mexidol is absent in the presence of bicuculline.

[Effect of tropoxin on cerebrovascular effects of meta-chlorophenylpiperazine and serotonin].

Experiments on rats showed that meta-chlorophenylpiperazine, as well as serotonin, decreases cerebral blood flow registered in internal carotid artery of narcotized animals. Therefore, this agonist of postsynaptic 5HT(2B/2C) receptors can be used for directed search of new antimigraine drugs. Tropoxin (10 mg/kg) substantially reduces constrictor reactions of cerebral blood vessels induced by meta-chlorophenylpiperazine.

[Cerebrovascular effects of afobazole under conditions of combined disorders of cerebral and coronary circulation].

Influence of afobazole on cerebral blood flow in rats under conditions of global transient ischemia of brain, experimental myocardial infarction, and combined disturbances of coronary and cerebral circulation was studied in comparison to intact and sham operated animals. It is established that afobazole (5 mg/kg) enhances blood flow in parietal region of cerebral cortex of rats after global transient ischemia of brain or experimental myocardial infarction more prominently than in intact and sham operated animals. Moreover, the cerebrovascular effect of afobazole substantially increases under conditions of combined vascular pathology of brain and heart and exceeds its action observed after the cerebral ischemia or myocardial infarction.

[Afobazole effect on cerebral circulation under hemorrhagic stroke model conditions].

Narcotized rats under hemorrhagic stroke model conditions exhibit a significant decrease in the cerebral flow in the region of contralateral cerebral hemisphere symmetric to the zone of lesion. Under these conditions, afobazole produced a significant increase in the local circulation in cerebral cortex, which was violated by hemorrhagic stroke. The cerebrovascular effect of afobazole was not manifested in cases of hemorrhagic stroke on the background of GABA receptor blocking by bicuculline.

[Nimodipine and experimental combined disorders of cerebral and coronary circulation].

The influence of nimodipine on the cerebral circulation of rats under conditions of global transient cerebral ischemia, myocardial ischemia, and combined disorders of cerebral and coronary circulation was experimentally studied in rats, in comparison to the intact and sham operated animals. It is shown that nimodipine (0.03 mg/kg) enhances circulation in the parietal region of the cerebral cortex to the same extent in both intact rats and those after global transient cerebral ischemia.