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The effect of flunarizine on the rheoncephalogram (REG) and on spontaneous electroencephalographic activity (EEG) was studied in acute experiments in cats. The following REG parameters were assayed: amplitude, anacrotic section of the curve and its relative part, and dicrotic index. EEG spectra were derived from 10-sec samples of EEG and the relative amplitudes were estimated at 2 Hz-intervals from 0-40 Hz. The REG study showed that flunarizine (2.5 and 5 mg/kg i.v.) caused an increase of the amplitude and a decrease of the anacrote, of its relative part, and the dicrotic index, changes indicating a lowering of the cerebrovascular resistance. EEG study showed a decrease of the amplitudes of the alpha-frequency band, and an increase of the fast-waves amplitudes, most pronounced at 5 mg/kg, changes showing enhancement of the activation processes in the brain cortex.

The effect of nicergoline on the rheoencephalogram (REG) and on spontaneous electroencephalographic activity (EEG) was studied in acute experiments in cats. The following REG parameters were assayed: amplitude, anacrotic section of the curve and its relative part and dicrotic index. EEG spectra were derived from 10-sec samples of ECoG and the relative amplitude was estimated at 2 Hz-intervals from 0-44 Hz. The REG study showed that nicergoline (0.05 mg/kg i.v.) caused an increase of the amplitude, and a decrease of the anacrote, of the relative part of the anacrote and the dicrotic index - changes indicating a lowering of cerebrovascular resistance. EEG study showed a decrease of the slow activities (theta and delta), and an increase of the fast activities (alpha and beta-1).

In acute experiments on cats under urethan anaesthesia and on dogs under chloralose-urethan narcosis the effect of the cinnarizine analogue Aligeron on local cortical cerebral blood flow (local CBF) and internal carotid blood flow was studied. The local CBF was recorded by means of a thermoclearance method using thermistor transducers. In addition the cortical pH and the arterial blood pressure were registered. For determination of internal carotid flow the flowmetric method was used accompanied by a simultaneous registering of heart rate and arterial blood pressure. Cinnarizine and papaverine were used as reference compounds. The results obtained show that Aligeron increases both the internal carotid flow (with 64% in a dose of 5 mg/kg) and the local CBF (with 30% in a dose of 1 mg/kg and 40% at 5 mg/kg). This effect is higher and longer-lasting than those of cinnarizine and papaverine.

The effect of As2 and Cinnarizin on cerebral circulation is studied on rabbits using the method of local cerebral rheography. Rheoencephalograms (REG) are recorded from the following brain structures; sensomotor cortex, substantia alba, poseterior hippocampus amygdala; nucleus caudatus and coliculus superior. Arterial blood pressure and ECG are studied simultaneously. Qualitative and quantitative analysis of the REG wave is made. Quantitative analysis involves the calculation of the following parameters: amplitude, anacrotic section of the curve and its relative part, spreading time and dicrotic index. The complex of REG-changes under the effect of the two drugs is very similar and suggests dilatation of the cerebral blood vessels. The difference is in the time of occurrence of the maximum effect: 5th min for As2 and 45th min for Cinnarizine.

The effect of Aligeron (1-benzhydril-4-allyl-piperazine dihydrochloride) on the cranial circulation was studied in dogs under chloralose-urethan anaesthesia. The parameters followed were: venous outflow from the confluence of the cerebral sinusses (CVO), cerebrospinal fluid pressure in cysterna magna (CSFP), systemic arterial blood pressure (BP) and pulse rate (PR). CVP was measured using the technique of Rapela and Green (1964). Aligeron was applied at doses of 5 and 10 mg/kg i.v. Papaverine hydrochloride was used as a reference compound. aligeron administration at a dose of 5 mg/kg led to quick increase of the CVO with a duration of the effect approximately 30 min. CSFP also increased in a similar way. BP and PR showed insignificant changes. The administration of 10 mg/kg did not lead to an increase of its effect on CVO. Papaverine (1 mg/kg i.v.) had a weaker effect than that of Aligeron. According to the classical concepts the changes observed in our experiments were due to the cerebral vasodilator effect of Aligeron which caused a fall in cerebrovascular resistance and an increase of the intracranial blood volume. Our experiments suggest that Aligeron influenced the resistance vessels more than the capacitance ones.

The cerebroprotective effect of nicergoline was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid ligation in rats, hemic hypoxia in rats and asphyxic anoxia in cats. Xanthinol nicotinate, vincamine, vinpocetine and cinnarizine were used as reference drugs. In hypobaric hypoxia and complete ischemia by decapitation the interaction of nicergoline with the effect of prostacyclin (PGI2) was investigated. Nicergoline showed cerebroprotective effect of varying potency in all the methods used except asphyxic anoxia. Nicergoline manifested a synergic effect with PGI2 shifting its anti-hypoxic dose-response curve to the left.

The influence of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the cerebral circulation and brain bioelectrical activity of cortex and mesencephalic reticular formation (RF) was studied in acute experiments on cats which were encéphale isolé preparations. The methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) were used. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and duration of the wave. The arterial blood pressure was followed continuously. The results show that upon piracetam administration (150 mg/kg i.v.) an improvement of the REG parameters of the cortex and RF is observed-an increase of the amplitude and decrease of the values of the anacrotic section of the curve and its relative part. The changes observed indicate a cerebro-vascular resistance decrease and give indirect evidence of cerebral blood volume increase. EEG data are characterized mainly by an increase of alpha-waves, both of cortex and RF. Suggestions for possible mechanism of action of piracetam are made.

The influence of orotic acid on cortical excitability processes and cerebral circulation was studied in acute experiments in cats. The effect on CNS excitability was assessed by examination of the cortical visual-evoked potentials and the recovery cycles. The flash-evoked responses were recorded from visual cortex (VC), associative cortex (AsC) and auditory cortex (AuC). The recovery cycles were determined as the ratio of the average response to the test stimulus and those to the conditioning stimulus depending on the interstimulus interval duration. For investigation of cerebral circulation the method of local cerebral rheoencephalography (REG) was used. The following REG parameters were assessed: amplitude, anacrotic sections of the curve and its relative part, and duration of the wave. The arterial blood pressure was monitored continuously. Orotic acid administration (50 mg/kg i.v.) induced a significant increase in the amplitude of the primary response from VC and AsC. Significant shortening of the peak latency of the second wave of the response in the VC was also observed. The recovery cycles examination showed a facilitation of the test response. The changes observed indicate an increase of excitability processes in the CNS. The REG changes after orotic acid indicate a cerebrovascular resistance decrease and increase in cerebral blood volume. It is assumed that increased cortical activity by orotic acid may lead to an improvement of cerebral circulation.

The effects of flunarizine and fezam on the local cerebral blood flow (LCBT) were examined by the hydrogen clearance with inhalation of hydrogen. The experiments were carried out on male nonbred cats under cetamine narcosis. The results showed that flunarizine (1 mg/kg i.v.) induced apparent enhancement of LCBF with 58% in comparison with the control values. The effect was read up to 60 min. The combined preparation fezam (100 mg/kg i.v.) caused considerable improvement of LCBF 30 min after inhalation with 63% in comparison with the control values. It is suggested that the observed effects are due to Ca-blocking action on cerebral vessels after flunarizine treatment as well as a reduction of cerebral-vascular resistance and influence on the metabolism after the combination fezam.

Various well-known agents with a favourable influence on cerebral circulation were used as a basis for creating new methods to asses the effects on this vascular region in experimental animals. A technique was worked out for radiocirculography and simultaneous radiometry, as well as for scanning and simultaneous radiometry of cat brain. Radiocirculography, followed by scintigraphy, proved to be among the best methods used for assessment of the effect of As2 on cerebral circulation. Simultaneous radiometry with the methods mentioned above had only orientational value. Radiocirculographic and scanning data after application of As2 in a dose of 10 mg/kg are close to those for nicotinic acid in a dose of 1 mg/kg. Similar to the data of the isotopic methods after application of As2 in a dose of 5 mg/kg are the results obtained with 5 mg/kg cinnarizin, which suggests a similar machanism of action.

The effect of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the local cortical cerebral blood flow (CBF) and oxygen balance in the brain was studied on cats anesthetized with ether-chloralose. The changes in local CBF were registered by means of the thermistor thermoclearance technique. pO2 and pCO2 were determined in blood samples from the femoral artery and superior sagittal sinus and arterio-venous differences of O2 and CO2 partial pressures (AVD-O2 and AVD-CO2) were calculated. The experiments were made on normoxic animals and on animals with slight hypoxia. Piracetam administration (100 mg/kg i.v.) leads to an increase in local cortical CBF corresponding to a change in the specific thermoconductivity of the brain of 0.6 . 10(-4) cal . cm-1 . sec-1 . degrees C-1. This effect is observed in 84% of the experiments with normoxia (arterial pO2 96.0 +/- 21.0 mm Hg) and in 40% of the experiments with slight hypoxia (arterial pO2 59.9 +/- 6.0 mm Hg). Changes in AVD-O2 and AVD-CO2 are not observed. Most probably the increase in CBF does not participate in the mechanism of the protective action of piracetam in hypoxia.

By means of the methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) the effect of piracetam (1-acetamide-2-pyrrolidone, Pyramem) on cerebral circulation and brain bioelectrical activity was studied in acute experiments on dogs. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and dicrotic index. The influence of the preparation on the spontaneous EEG was studied by means of surface electrodes, pH, pO2, and pCO2 were determined in blood samples from femoral artery and superior sagittal sinus and arterio-venous differences of O2 (AVD-O2) and CO2 (AVD-CO2) were calculated. The arterial pressure and ECG were followed continuously. The results showed that after piracetam administration (100 mg/kg i.v.) an improvement of the REG parameters is observed: increase of the amplitude and decrease of the values of the relative part and dicrotic index. The changes observed indicated cerebro-vascular resistance decrease and increase of the cerebral blood volume. The AVD-O2 increased and the negative AVD-CO2 decreased. The EEG data indicated an improvement in the functional state of the brain cortex. Suggestions as to mechanism of piracetam effect and the usefulness of the methods were made.