Biomedical subjects

R Nikolov

Publications and source records attributed to R Nikolov.

At least 37 records · Page 2Linked to original sources

PubMed1989

Streptozotocin-induced diabetes in rat. III. Antioxidant protection of vascular complications by flunarizine and aligeron.

In rats with streptozotocin-induced diabetes antioxidant protection of diabetic angiopathy was performed by flunarizine (10 mg/kg/day) and aligeron (10 mg/kg/day), applied intraperitoneally during 2.5 months of diabetes. Diabetic vascular complications were assessed by morphologic determination of PAS-positive mucopolysaccharides and measurement of vascular wall thickness in addition to quantitative estimation of lipid hydroperoxides, thromboxane A2/prostacyclin disbalance and plasma beta-thromboglobulin changes. Both drugs prevented development of diabetic angiopathy in rats by inhibition of lipid peroxidation, prostanoid synthesis and platelet activity, but the effect of flunarizine was more pronounced, which could be explained by its additional blocking effect of abnormal calcium flux into vascular cells. The free radical scavenging action of flunarizine and aligeron was investigated.

Animals↗

PubMed1989

Effects of nicergoline in experimental models related to pathogenesis of migraine.

The effect of nicergoline on cerebral blood flow (CBF), cerebrovascular resistance, the constriction of cerebral vessels caused reflectorily or by 5-hydroxytryptamine (5-HT) and on the transport of 5-HT in rat brain synaptosomes was studied using different experimental models. Nicergoline reduced cerebrovascular resistance in the carotid and vertebrobasilar system. The drug decreased carotid blood flow and local cortical CBF, preceded in some experiments by short-lasting CBF increase. Nicergoline almost completely inhibited brain vessels responses in the carotid and vertebrobasilar systems after tibial nerve stimulation. Simultaneously, inhibition of reflectory discharges of the sympathetic nerves was observed. Nicergoline showed an antiserotonin action by antagonizing the 5-HT effect on the cerebral circulation and inhibiting 5-HT-induced constriction of isolated rabbit basilar artery. The inhibition of uptake and enhancement of the release of 5-HT from brain synaptosomes indicates its ability to affect neuronal transmission in serotoninergic neurons. The effects of nicergoline are probably involved in the realization of its antimigraine action.

Animals↗

PubMed1989

Prostacyclin as a cerebroprotective agent against brain hypoxia.

The cerebroprotective effect of prostacyclin (PGI2) was studied using the following methods: hypobaric hypoxia in mice, anoxic hypoxia in mice, complete ischemia by decapitation in mice, hypoventilation hypoxia in cats, and hypovolemic hypoxia in cats. PGI2 induced a dose-dependent prolongation of the survival time of mice, when administered either I.C.V. (0.001-10/micrograms/mice), I.V. (0.5-500/micrograms/kg), or I.P. (50-500/micrograms/kg). In the experiments on cats PGI2 (250 ng/kg/min I.V.) led to a significant improvement of the hypoxic ECoG. In another series of experiments, an interaction of some cerebroprotective agents with the anti-hypoxic effect of PGI2 was investigated. Piracetam, meclofenoxate, nicergoline, naftidrofuryl, cinnarizine, and nifedipine shifted the anti-hypoxic dose-response curve of PGI2 to the left indicating synergistic interaction. The results obtained suggest the function of PGI2 as a cerebroprotective prostanoid in brain hypoxia.

Animals↗

PubMed1989

[Assessment of local cerebral blood flow by the hydrogen clearance method. I].

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.

Animals↗

PubMed1989

Comparative evaluation of the Ca2+-antagonistic activity of some Bulgarian vasodilating agents and of known Ca2+-antagonists on K+-depolarized smooth muscle from guinea-pig taenia coli.

The informative value of the experimental model for inhibition of the effect of the Ca2+-induced contraction in 40 mM K+-depolarized smooth muscle from guinea-pig taenia coli, is investigated in order to determine the intensity of the Ca2+-antagonistic activity of different agents on the voltage-dependent calcium channels. The Ca2+-antagonistic activity of two original Bulgarian vasodilating agents - piperazine derivatives (aligeron and P-11) possessing potential Ca2+-blocking properties, is compared with the activity of known Ca2+-antagonists which are widely used in clinical practice (verapamil, nitrendipine, cinnarizine and flunarizine). Cumulative dose-response curves of CaCl2 (0.1-3.0 mM) in Ca2+ free K+-depolarizing solution are recorded in advance and 30 min after the administration of the test-substances. On the basis of the intensity of the Ca2+-antagonistic activity, determined by their pA2 values, the substances investigated are ordered as follows: nitrendipine greater than verapamil greater than cinnarizine greater than or equal to flunarizine greater than aligeron greater than P-11. On the background of the CaCl2-induced (1 mM) long-lasting contraction, the substances tested manifest qualitatively different relaxing effects, which suggest different mechanisms of action of the Ca2+ antagonists studied, as well as the significance of the experimental protocol in evaluating the intensity of the Ca2+ antagonistic activity.

Animals↗

PubMed1988

Effect of nicergoline on learning and memory.

The anti-amnestic action of nicergoline was studied using the following experimental methods for learning and memory impairment, based on passive avoidance response: amnesia induced by maximal electroshock in mice, scopolamine-induced amnesia in mice and amnesia by paradoxical sleep deprivation in rats. Piracetam, meclofenoxate, pyritinol, deanol and phenazepam were used as reference drugs. The results show that nicergoline demonstrates well-expressed anti-amnestic effect manifested by reducing the amnestic effect of maximal electroshock, scopolamine or paradoxical sleep deprivation, its effect being equal to or more pronounced than piracetam, meclofenoxate, pyritinol, deanol and phenazepam.

Amnesia↗

PubMed1987

Cerebroprotective effect of nicergoline and interference with the anti-hypoxic effect of prostacyclin.

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.

Animals↗

PubMed1985

Effect of piracetam on the electrocorticogram after traumatic brain oedema in cats.

The effect of piracetam on the electrocorticogram changes caused by experimentally-induced traumatic brain oedema in cats has been studied. The trauma was evoked by sticking a needle through the parietal associative cortical area. The electrocorticogram amplitude and frequency depression of the injured cortical area was eliminated and the bioelectrical activity restored to a normal pattern 22.4 +/- 10.3 min after a single dose of piracetam (100 mg/kg i.v.). The results indicate that piracetam recovered the cortical bioelectrical activity disturbed by experimentally-induced traumatic oedema. The beneficial effect of piracetam is probably due to an optimization of the functional state of the brain since piracetam acts as a nonspecific activator of brain excitability.

Animals↗

PubMed1985

[Electron microscopic study of the myocardium in 2 cases of primary systemic amyloidosis].

The authors describe two cases with primary systemic amyloidosis advancing with the picture of progressing cardiac insufficiency, clinically not distinguished. Electron microscopic study of myocardium was performed. The ultrastructural data indicate that the most likely source for synthesis of amyloid in myocardium, in primary systemic amyloidosis, are the active fibroblasts, established in interstitium.

Aged↗

PubMed1985

Antagonistic activity of aligeron and papaverine against different smooth muscle stimuli.

The antagonistic action of aligeron as compared to that of papaverine against different smooth muscle stimuli was studied in experiments in vitro. Three series of experiments were conducted: study of the antagonistic action against experimental spasms of isolated organs caused by different spasmogens; determination of the type of antagonism to adrenaline in isolated vas deferens preparation; and study of the antagonistic action against vasoconstrictor effects of noradrenaline and adrenaline in isolated perfused rabbit renal artery. Aligeron showed a broad spectrum of antagonistic action against different spasmogens in different isolated organs. Its effect was more pronounced than that of papaverine. The antagonism was of the non-competitive type. The experiments on isolated perfused rabbit artery showed the antagonistic action of aligeron against the vasoconstrictor effects of noradrenaline and adrenaline. The results suggest the clinical use of aligeron in conditions associated with increased release of these vasoactive substances.

Animals↗

PubMed1984

Study on the anti-hypoxic effect of cinnarizine and its interaction with prostacyclin.

The anti-hypoxic effect of cinnarizine was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice and hemic hypoxia in rats. Papaverine, xanthinol nicotinate and naftidrofuryl were used as reference drugs. In hypobaric and anoxic hypoxia the interaction of cinnarizine with the effect of prostacyclin (PGI2) was investigated. Cinnarizine showed an anti-hypoxic effect in all the methods used. It was more effective in hypobaric and anoxic hypoxia, in incomplete ischemia by decapitation, and less effective in hemic hypoxia. Cinnarizine potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left. Suggestions as to the possible mechanism of anti-hypoxic action of cinnarizine are made.

Animals↗

PubMed1984

Anti-hypoxic effect of piracetam and its interaction with prostacyclin.

The anti-hypoxic effect of piracetam was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid occlusion in rats and hemic hypoxia in rats. Cinnarizine and vinpocetine were used as reference drugs. In hypobaric hypoxia, anoxic hypoxia, and complete ischemia by decapitation the interaction of piracetam with the effect of prostacyclin (PGI2) was investigated. Piracetam showed anti-hypoxic effect in all the methods used. Its effect was greater than that of cinnarizine and similar to that of vinpocetine. Piracetam potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left.

Animals↗

PubMed1984

Anti-hypoxic effect of centrally and systemically administered prostacyclin (PGI2).

Prostacyclin (PGI2) induced a dose-dependent prolongation of survival time of mice subjected to hypoxic and anoxic hypoxia, when administered either intracerebroventricularly (i.c.v., 0.001-10 micrograms/mouse), intravenously (i.v., 0.5-500 micrograms/kg) or intraperitoneally (i.p., 50-500 micrograms/kg). The effects of a single dose of 50 micrograms/kg i.v. or i.p. and of 1 microgram/mouse i.c.v. persisted for about 30 min. The anti-hypoxic effect of PGI2 is most likely due to an action upon the CNS.

Animals↗

PubMed1984

Arachidonic acid cascade and anti-hypoxic drugs.

The anti-hypoxic effect of drugs that inhibit different steps of arachidonic acid metabolism was studied using an experimental model of acute hypobaric hypoxia in mice. The drugs investigated were chloroquine, betamethasone, chlorpromazine (phospholipase A2 inhibitors), ketoprofen (cyclo-oxygenase inhibitor) and imidazole (TxA2 synthetase inhibitor). Prostacyclin (PGI2) and PGF2 alpha were also studied. The results show that all the inhibitors of arachidonic acid metabolism manifest an anti-hypoxic effect of a various degree. PGF2 alpha had a deleterious effect, and PGI2 showed a marked anti-hypoxic effect. The results suggest that it is advantageous to search for anti-hypoxic drugs among the blockers of arachidonic acid cascade.

Animals↗

PubMed1984

Inhibition of phospholipase A2 in vitro by some anti-hypoxic drugs.

The effect of the anti-hypoxic drugs piracetam, nicergoline, papaverine, cinnarizine and aligeron on the activity of bee venom phospholipase A2 was studied in experiments in vitro. The pH-stat titration method of Grossmann et al. was used. All the drugs studied inhibited to a various degree the activity of phospholipase A2 in vitro. The most potent drug was nicergoline and the least potent was papaverine. Taking into account that the activity of phospholipase A2 is stimulated in hypoxia, the results make us believe that the inhibition of phospholipase A2 might play a certain role in the anti-hypoxic effect of the drugs studied.

Arachidonic Acid↗

PubMed1984

Piracetam and brain excitability. An electrophysiological study in cats.

The effect of piracetam on the excitability of the brain has been examined in cats by electrophysiological approaches: spontaneous electrocorticogram (ECoG), visual evoked potentials (VEPs) and their recovery cycles in some brain structures (visual and associative cortex, lateral geniculate body, centrum medianum thalami and mesencephalic reticular formation). Piracetam (100 mg/kg i.v.) increased the spectral power of ECoG and particularly in the associative cortex for the frequency bands of 10-12 and 19-22 Hz. Piracetam decreased the early components and facilitated the late components of VEPs predominantly in the associative cortex. Changes were found in the recovery cycles too, namely, facilitation and shortening of recovery in all structures studied except in lateral geniculate body. The data suggest that piracetam acts as a non-specific activator on the excitability thus optimizing the functional state of the brain.

Animals↗

PubMed1983

Effect of aligeron and cinnarizine in models of general and local depression of the cortical bioelectrical activity in cats.

The effect of aligeron (5 mg/kg i.v.) and cinnarizine (10 mg/kg i.v.) on general and local depression of cortical bioelectrical activity was studied in acute experiments on cats. Asphyxic anoxia and hypoventilation hypoxia were used as models of general depression. Local depressions were caused by topical application of potassium chloride (KCl) and adenosine-5'-monophosphate (AMP) on the cortex. In hypoventilation hypoxia aligeron and cinnarizine increased cortical resistance to hypoxia and accelerated the recovery of cortical bioelectrical activity. In KCl- and AMP-induced depressions the drugs showed a protective effect manifested in a decrease of the degree and duration of the depression. In asphyxic anoxia their effect was insignificant.

Animals↗

PubMed1983

Anti-hypoxic effect of indomethacin and its interaction with prostacyclin.

The anti-hypoxic effect of indomethacin (1-10 mg/kg) was studied using the following experimental methods: asphyxic anoxia in cats, hypobaric and anoxic hypoxia in mice, incomplete ischemia by bilateral carotid occlusion and hemic hypoxia in rats. In hypobaric and anoxic hypoxia the interaction of indomethacin with the effect of prostacyclin (PCl2) was investigated. Indomethacin showed an anti-hypoxic effect in all the methods used: it enhanced anoxia resistance index in asphyxic anoxia and significantly increased survival of rats and mice subjected to experimental hypoxia. Indomethacin potentiated the effect of PGl2, shifting the anti-hypoxic dose-response curve of PGl2 to the left. The possible mechanism of action of indomethacin in relation to cyclo-oxygenase inhibition is discussed.

Animals↗