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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.

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. In rats with experimental myocardial infarction and combined vascular pathology of brain and heart not all of the compounds mentioned acbove with GABA-ergic mechanism of action stimulate the cerebral blood flow. Thus, both similarity and differences in cerebrovascular effects of these compounds have been found, which depend on the initial state of organism and the vascular pathology of brain and/or heart. The obtained results show good prospects for this direction of research.

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.

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.

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.

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

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. This effect is not neutralized by bicuculline.

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. It is established that N-[2-(adamant-2-yl)aminocarbonylmethyl]-N'-[3-(diethylamino)propyl]-4-nitrobenzamide has prominent antiarrhythmic activity and is more safe than other antiarrhythmic drugs of class I (lidocaine, ethmosine, novocainamide), class IV (verapamil), and class III (cardiocyclide).

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. In the same dose, adamantane derivate significantly decreases mortality in rats under conditions of hypergravity ischemia. The cerebrovascular effect of adamantane derivate is abolished by bicuculline (GABA-A receptor blocker), which is evidence for a GABAergic component in the mechanism of the cerebrovascular action ofadamantane derivate.

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. It is established that the cerebrovascular activity of the epiphyseal hormone is mediated by GABA-A receptors of cerebral vessels. Melatonin (in doses of 1.0 and 5.0 mg/kg) significantly increased survival of rats under conditions of hypergravity ischemia.

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. Under conditions of the combined vascular pathology of brain and heart, the cerebrovascular effect of GABA-DHED conjugate is inhibited by bicuculline, which is evidence for the involvement of GABAergic mechanisms in the drug action upon cerebrovascular tone.

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.

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.

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.

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.

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.

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. The effect was observed during both prophylaxis and treatment of the model disorder with this drug.

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.

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. The obtained results demonstrate that afobazole increases the cerebral blood flow not only under conditions of global transient cerebral ischemia, but on the hemorrhagic stroke model as well, which is probably related to a mediated drug effect on the GABA receptor complex.

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. Under conditions of experimental myocardial infarction, the cerebrovascular effect of nimodipine was significantly decreased in comparison to that in intact and sham operated animals. In contrast to intact and sham operated rats and the rats with myocardial infarction, there were no signs of cerebrovascular activity of nimodipine in animals with combined disorders of coronary and cerebral circulation. A new approach to the search for and investigation of pharmacological agents for the treatment of combined disturbances of cerebral and cardiac circulation is proposed.

Experiments in anesthetized rats showed that global transient brain ischemia caused a significant decrease in cerebral blood flow in rat cerebral cortex and reduced the stress protein HSP70 level in striatum. Afobazole administration restored the cerebral blood supply disturbed by ischemia and increased the stress protein HSP70 synthesis in striatum.

The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral haemodynamics and thrombocyte aggregation were evaluated and compared to these of docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to significantly enhance the cerebral circulation in rats with a model of global transient cerebral ischemia, as compared to the intact animals. Administered alone, DHED increased the blood supply of both intact and ischemic brains to an equal extent. The GABA-DHED conjugate demonstrated the antiaggregative activity, but the effect was less expressed than that of DHED alone.

The influence of afobazole on the accumulation of free radical oxidation products (reactive oxygen species, ROS) and on the activity of antioxidative enzyme catalase was studied in striatum and cortex of rats under cerebral ischemia damage conditions. Afobazole showed a tendency to decrease the extent of ROS accumulation in the cortex. In striatum, the intensity of ROS accumulation in rats after ischemia wasa reliably lower as compared to that in control rats, but afobazole produced a partial recovery of this parameter. Afobazole induced an increase in the catalase activity in the cortex of rats with ischemia. In contrast, afobazole did not change the activity of this enzyme in striatum (where it was also decreased by ischemia). Thus, afobazole increased the resistance of neuron membrane structures to free radical oxidation in cortex and striatum and stimulated the catalase activity in the cortex in rats with global reversible cerebral ischernia.

The effects of the antimigraine drug tropoxin and its main molecular fragments - tropan and 3,4,5-trimetoxybenzoate (TMB) - on the serotonin sensitivity of postsynaptic neuronal membrane in rat brain sensorimotor area has been studied using a microionophoretic (MIP) technique. All the three substances significantly reduce the excitatory neuronal response to serotonin, which is manifested by an increase in the rate of the spontaneous action potentials. With respect to the antiserotonin effect, the substances can be arranged in the following order: tropoxin > tropan > TMB. The sum of the effects of tropan and TMB (for both simultaneous and separate action upon the target cells) was significantly lower than the effect of tropoxin in all doses (MIP currents). It is concluded that a pronounced antiserotonin effect of tropoxin is produced only provided that the entire molecular configuration is retained. Tropan and TMB, being tropoxin metabolites, are probably capable of prolonging the antimigraine action upon the decay of tropoxin in the organism. A relationship between the structure and action of serotonin receptor blockers of the tropan series is discussed.

The effect of the new antimigraine drug tropoxin - the serotonin receptor (5-HT2) antagonist - on the human platelet aggregation in vitro induced by ADP (1 x 10(-5) M) and epinephrine (2.5 x 10(-6) M) was studied. Tropoxin reliably inhibited the ADP-induced platelet aggregation in a concentration range of 0.01 - 7 mg/ml. A significant inhibition effect with respect to the epinephrine-induced platelet aggregation was observed in a drug concentration range of 2 - 7 mg/ml, although a reliable antiaggregant activity was also observed below 2 mg/ml. A bolus administration of tropoxin (10 mg/kg) in rabbits decreased the ADP-induced platelet aggregation ex vivo by a factor of 1.2 - 1.4. The effect appeared 45 min after treatment and was observed during subsequent 30 min.

The role of GABAergic mechanisms in realization of the effects of afobazole and picamilon on the cerebral circulation was studied in rats. It is found that the cerebrovascular effect of afobazole significantly decreases on the background of the GABA receptor antagonists bicuculline and picrotoxin. This is evidence of an important role of the GABA system in the its cerebrovascular and neuroprotective activity of afobazole. The results of experiments with picamilon showed that the cerebrovascular effect of this drug is not affected by receptor blocking with bicucullin. However, the blocking of chloride channels of the GABA receptors by picrotoxin significantly decreased the effect of picamilon on the cerebral blood flow.

The influence a series of anxiolytics (tranquilizers) on behavioral disturbances was studied in outbread white male rats with cerebrovascular pathology modeled by ligation of common carotid arteries. All studied anxiolytics (diazepam, buspirone, mexidol) exhibited more of less pronounced protective action with respect to the pathology studied. The most significant protective effect was produced by the atypical anxiolytic mexidol. Special features of the effect of mexidol are probably explained by combination of several effects (anxiolytic, nootrope, antioxidant, and antihypoxant). in the pharmacological activity spectrum of this drug.

The selective anxiolytic drug afobazole administered in a dose of 5 mg/kg increased the cerebral blood flow in rats. The effect was more pronounced in rats with global reversible cerebral ischemia than in intact animals. The ischemia model was caused by occlusion of both common carotid arteries for 120 min with simultaneous reduction of the arterial pressure to 40-50 mm Hg through blood-letting. Afobazole also significantly increased the survival of rats with cerebral ischemia model caused by ligation of both common carotid arteries, which was evidence of the neuroprotector activity. Apparently, the ability of afobazole to improve the cerebral blood flow in ischemized rat brain is an important factor in realization of the neuroprotector activity.

The physiological metabolite esafosfina (fructose 1,6-diphosphate) influences the cerebral circulation of intact male rats. Injected intravenously in a dose of 250 mg/kg, esafosfina improved both the blood supply to brain and the local blood flow in the parietal region. Under the conditions of global transient cerebral ischemia, the cerebrovascular effect of the drug tends to increase. Esafosfina produced dissimilar changes in the arterial blood level, which could be explained by various basic status of the test animals. The pronounced cerebrovascular activity of esafosfina plays a key role in its neuroprotector effect.

Cytamines (hepatamin, epifamin, and suprenamin) administered in various combinations increase the working ability of high-rank athletes in experiments. These cytamines also potentiate the effects of apilak, ecdystene, vitamax, and essentiale preparations on the exercise tolerance.

The paper is devoted to the role of GABA system in the pharmacotherapy of ischemic brain injuries. In an analysis of the neuroprotector activity of GABA-mimetics, both their involvement in the maintenance of a balance between exciting and inhibiting processes and participation of the GABAergic mechanisms in regulation of the cerebrovascular tone are considered because proper blood supply is an important factor in the successful therapy of patients with ischemic brain injuries. Data available in the literature and the results of original investigations are summarized to assess the cerebrovascular and neuroprotector properties of GABA, as well as agonists and modulators of GABA receptors (muscimol, picamilon, phelbamate, clomethiazole, etc.). Particular attention is given to the neutroprotector and cerebrovascular activity of a new drug composition GABA-mimetic pirrolidone and pyroglutamic acid. This drug is capable of improving the cerebral blood supply, limiting the zone of ischemic injury, preventing an increase in the level of lactate and lipid peroxidation products, modifying nitric oxide content, and restoring the psychoneurological status of experimental animals with ischemic brain injury models.

A new drug composition containing pyroglutamic acid and pyrrolidone produces a significant effect on the cerebral circulation in rats with global recurrent brain ischemia and in a model ischemic state under high radial gravitational overload. In the former case, the new drug increases the blood circulation in rats with the global ischemic damage to a greater extent than in the intact control group. Pretreatment with the pyroglutamic acid--pyrrolidone composition produced a 2-2.5-fold increase in the survival of rats in the ischemic state caused by the radial gravitational overload. The data obtained show evidence of a substantial neuroprotector action of the new drug composition.

A series of original dopaminamides of polyunsaturated fatty acids were synthesized and characterized with respect to antiaggregant and cerebrovascular stimulant properties. It was established that dopaminamides of linolic, dimethyllinolic, docosapentaenoic, docosahexaenoic (DHEA) and stearidonic (C18:4 and C18:3) acids decrease ADP and arachidonic acid (AA) induced human thrombocyte aggregation in vitro. The most pronounced antiaggregant effect was observed for DHEA dopaminamide: in a dose of 10 mg/kg, this agent produced a significant decrease in the AA induced thrombocyte aggregation. DHEA per se in the same dose increases the activated partial thromboplastin time (APTT), while not affecting the prothrombin time. The synthesized dopaminamides of arachidonic, eicosapentaenoic, and docosahexaenoic acids stimulate local circulation in the cerebral cortex. The most pronounced cerebrovascular effect was also produced by DHEA dopaminamide.

A drug composition containing pyroglutamic acid and pyrrolidone produces a significant effect on the cerebral circulation in rats and cats, which is manifested by increased cerebral blood flow and by a dose-independent improvement of the microcirculation. The cerebrovascular effects were similarly pronounced in both rats and cats which indicates that the drug action is independent of the animal species. The drug combination studied did not exhibit antiserotonin activity. The data obtained show evidence of a substantial contribution of the cerebrovascular component to the neuroprotector action of the drug composition studied.

Effect of the new antimigraine drug tropoxin on the EEG profile was studied in MR and MNRA rats with genetically determined high and low levels of emotionality, respectively. In MR rats, tropoxin decreased the number of the bioelectric activity parameters changed by the stressor action (0.9% NaCl, i.p.). The drug reduced the spectral power in the EEG delta band, and increased that in the theta, beta-1, and beta-2 bands. This was evidence of the central stimulating action and the possible enhancement of the exploratory activity. In MNRA rats no changes in bioelectric activity were observed in the low-frequency delta and theta bands, while the spectral power in the beta-1, and beta-2 bands showed a decrease. It was concluded that a neural component is present in the mechanism of the tropoxin action, which may play an important part in the therapeutic effect of the new drug.

The effect of serotonin on the brain blood supply was studied in rats before and after ischemic damage. The ischemic damage, induced by ligation of the middle meningeal artery, markedly enhanced the constrictor effect of serotonin on the brain vessels. Tropoxin, a 5HT2 receptor blocker, completely eliminated these cerebrovascular effects of serotonin.

The effect of dopamine on the local cerebral blood flow in parietal brain cortex region of rats was studied in conditions of local ischemia induced by middle cerebral artery occlusion. Registration of the local cerebral blood flow was performed on a ALF-21 laser doppler flowmeter ("Transonic System Inc.", USA). Dopamine produces a pronounced effect on cerebral circulation in conditions of local brain ischemia thus causing a significant increase in blood flow both in ischemic and intact hemispheres. The effect is observed both in the acute stage of ischemic brain injury and in the remote period of brain ischemia.

Electrical stimulation of the cervical sympathetic ganglion and norepinephrine increase the tonus of the cerebral vessels in intact animals. This points to the significant role of adrenergic mechanisms in regulation of blood circulation in the brain. Local ischemic affection of the brain removes the vasoconstrictor effects of stimulation of the cervical sympathetic ganglion and norepinephrine. Analysis by means of dihydroergotamine suggests that ischemia of the brain disturbs the property of alpha-adrenoceptors of the cerebral vessels to increase the tonus of the latter in response to adrenergic effects.

The search for serotonin antagonists with cerebrovascular activity was conducted among newly synthesized aromatic and heteroaromatic ethers of tropinone oxim. One of these compounds, namely, hydrochloride-3(3,4,5-trimethoxybenzoiloxiimino-1)-8-methyl-8-a zab icyclo [3,2,1] octane, called tropoxin, prevented the development of serotonin-induced constriction of cerebral vessels in vitro and in vivo experiments. This effect was demonstrated also in experiments with oral administration of the drug. Tropoxin was found to possess affinity for 5-HT2 receptors of the rat brain. Tropoxin surpasses the anti-migraine drug methysergide in antiserotonin cerebrovascular activity. This allows tropoxin to be recommended for study as a means for the treatment of migraine.

A modified rat model of ischemic brain injury caused by ligation of the middle cerebral artery is proposed. The time course of morphological changes in brain tissues was studied and bilateral cerebral circulatory disorders, hypoxic cortical neurocytic damages followed by intracellular regeneration, as well as metabolic and structural changes not only in the cortical neurocytes, but in the conduction paths and synaptic terminals. Nimodipine had no effect on blood supply to the ischemic brain either early or late in ischemic brain injury after ligation of the middle cerebral artery.

The permeability through the blood-brain barrier of N-(4-hydroxy-3,3 dimethyl-2-oxo-1-butiryl) gamma-aminobutyric acid calcium salt, a new neurotropic drug calcium ketohomopantothenate (KPA-Ca), was studied in comparison with that of calcium homopantothenate, pantogam (P) Liquid chromatography analysis showed that after oral administration of KPA-Ca and P both forms of these agents, namely, oxy- and keto- derivatives of homopantothenic acid, were found in the brain of experimental rats, the KPA-Ca (ketoform) content being higher. Pharmacological studies showed that KPA-Ca penetrates the blood-brain barrier in greater amounts and causes a higher effect on the rate of cerebral blood flow when it is administered per os in a dose of 50 mg/kg.

Experiments conducted on Wistar rats under general anesthesia using the Doppler ultrasonic method showed that flunarizine caused a slowly developing (for 20 min), moderate (25%), and prolonged (90 min) increase of the blood flow in the middle cerebral artery. In the common carotid artery the drug induced two-phase changes in blood circulation. The initial increase in the blood flow was replaced by its reduction below the basic level.

Experiments on rats with the use of ultrasonic techniques demonstrated that serotonin causes an initial significant decrease in the blood flow in the channel of the middle cerebral artery followed by a mild increase in the blood supply to the brain. It was shown in in vivo experiments that nimodipine and nifedipine do not prevent the development of serotonin-induced constriction of the vessels of the middle cerebral artery channel. At the same time, the cerebrovascular effects of nimodipine and nifedipine are significantly weakened under the action of serotonin.

A model of local cerebral ischemia induced by ligation of the middle cerebral artery, which is a modification of the techniques proposed by A. Tamura and others, is suggested. It allows experiments to be conducted on conscious animals with appraisal of the morpho-functional state of the nervous system. Ligation of the middle cerebral artery caused a marked decrease (by 85 +/- 9%) in the blood flow in the temporal area of the cerebral cortex. The use of this method will promote a purposeful search for drugs for the treatment of patients with ischemic disorders of cerebral circulation.

Experimentally, metisergide largely prevents and attenuates the development of cerebrovascular constrictive responses evoked by serotonin. Propranolol and tolphenamic acid alleviate decreases in the volumetric velocity of brain blood flow, which are induced by serotonin in half of the total number of experiments whereas in the other experiments these agents show no antiserotonin cerebrovascular properties.