PubMed Health⌕ Search

Biomedical subjects

V D Petkov

Publications and source records attributed to V D Petkov.

At least 55 records · Page 3Linked to original sources
PubMed1989

Biological tests for opiate activity of newly-synthesized compounds--opioid peptides and cyclic beta-diketones.

A group of newly-synthesized (Leu5) enkephalinamides and their derivatives, with incorporated D-amino acids, as well as a group of cyclic beta-diketones from the group of 1, 3-indandiones, were partially pharmacologically characterized in experiments in vivo and in vitro. The substances studied, applied subcutaneously in doses of 50 to 1250 micrograms/kg bogy mass in mice, did not induce symptoms of acute and late toxicity. According to the parameters of the neuropharmacological screening tests performed, no significant differences were observed between the mice treated with the agents tested and the control mice. All five agents investigated significantly shortened the duration of hexobaribital-induced sleep. In the experiments using the conflict test after Vogel et al. (1971), (D-Ala2, D-Leu5) enkephalinamide induced a behavioural effect which can be qualified as anxiolytic. The same analogue also manifested a marked analgesic effect with the two tests used: hot plate test and the peritoneal test with glacial acetic acid. The cyclic beta-diketones-(methindiones) tested also manifested good analgesic effect with both test. (D-Ala2, D-Leu5), enkephalinamide strongly reduced the electrically induced contractile responses of the ileum. This effect was completely prevented by naloxone. The fact that (D-Ala2, D-Leu5) enkephalinamaide, known as a selective agonist of the delta-opiate receptors, proved to be particularly active suggests that both mu- and delta-type opiate receptors exist in the guinea-pig ileum. The pronounced analgesic effect of the leucine-enkephalinamide analogue with two substituted D-amino acids and of the two cyclic beta-diketone methindiones opens up new possibilities for synthesizing efficient analgesic agents.

Analgesics↗
PubMed1989

Quantification of the synapses in the hippocampus of aged rats.

The synapses in the stratum lacunosum-molecular (str. L-M) of CA1 hippocampal field in 3-month old and 24-month old rats were examined using quantitative ultrastructural methods. No significant difference in the density of synapses and postsynaptic dendritic spines was found between the two age groups. The area of presynaptic terminals and postsynaptic dendritic spines was decreased slightly but significantly in the group of aged as compared to that in the group of young-mature rats. The vesicle number per presynaptic terminal, per area of presynaptic terminals and per volume of neuropil was not changed while the vesicle number per area of synaptic contact zones (SCZ) was increased in the group of aged rats. The mean length, total length and total surface of SCZ were diminished in the group of aged as compared to those in the group of young-mature rats. The same width of the str.radiatum and str.L-M in the two age groups showed that there was no any shrinkage of the neuropil in aged rats. The quantitative alterations in the synapses were accompanied by an increased number of dense and lamellar bodies in presynaptic terminals as well as with a presence of hypertrophic astroglial processes.

Aging↗
PubMed1989

Learning and memory effects of four newly-synthesized aniracetam analogues.

Four new analogues of the pyrolidine derivative with nootropic action--aniracetam--were synthesized using classical methods. The effects of the newly-synthesized compounds were tested using the step-through method for passive avoidance with negative reinforcement and the method of habituation of exploratory activity in the Opto-Varimex apparatus. Two series of experiments were performed using the step-through method: in one series aniracetam (Anc) and its analogues p-H and p-Cl were applied twice daily in a dose of 50 mg/kg for 7 days prior to the training session; retention tests were made 3 h, 24 h and 7 days after the training session. In the other series of experiments the Anc analogues p-P (in single daily doses of 10, 50 and 250 mg/kg) and p-F (in a single daily dose of 50 mg/kg) were applied for 5 days prior to the training session; memory tests were performed 24 h and 7 days after the training session. In one of the experimental series in Opto-Varimex, after 5-min recording of the horizontal, vertical and rotatory movements of each rat, the various groups of animals received 20, 100 or 300 mg/kg from each of the agents tested (Anc, p-Cl and p-H). Tests for habituation were performed 7 days later. The other series of experiments in Opto-Varimex included groups of rats receiving 50 mg/kg Anc, p-Cl and p-H twice daily for 7 days. The three types of movement were recorded for 5 min in the Opto-Varimex after the last dose of the substances tested. All substances were administered orally. The results obtained (longer time spent by the animals in the illuminated section when the step-through method was used and enhanced habituation in the Opto-Varimex experiments) suggest that the substances tested improve the memory, mainly through improving the process of consolidation of the memory traces.

Animals↗
PubMed1988

Age-related changes in brain neurotransmission.

In experiments on 2-, 10- and 22-month-old rats it was found that the Bmax values of dopamine (DA2), serotonin (5-HT1) and enkephalin (Enk) receptors as well as the 5-HT level in the three brain regions (cortex, striatum and hypothalamus) decreased with age; the DA level in the brain cortex and striatum and the noradrenaline (NA) content in the brain cortex decreased, while the NA level in the striatum and the 5-hydroxyindolacetic acid (5-HIAA) level in the brain cortex and the striatum as well as the MAO-T and MAO-A activities in the three brain structures increased. It is suggested that these and other changes observed in brain neurotransmission are an important element in the neurochemical bases of the age-related changes in behavior.

Aging↗
PubMed1988

Memory effects of the combination of medazepam with nootropic agents.

Experiments were made on rats using step-through passive avoidance method to study the effect of the benzodiazepine medazepam (Mz) on the retention of the memory traces during tests on the 3rd hour, 24th hour and 7th day after training, as well as the influencing of this effect by the nootropic agents meclofenoxate (Mf), aniracetam (Anc) and Euclidan (Eucl.). All substances tested (Mz in a dose of 5 mg/kg weight, Mf - 100 mg/kg, Anc and Eucl - 50 mg/kg), applied both independently and in combination, were administered orally for six days prior to the training. Mz was found to impair the retention of the memory traces in all three tests. Meclofenoxate totally eliminated the memory-impairing effect of Mz. A marked antiamnestic effect of both Anc and Eucl was observed in similar experiments with scopolamine-induced (2 mg/kg i.p.) amnesia. Bearing in mind the results of other behavioural and biochemical studies, including radioligand tests, an attempt is made to justify the idea that the basic mechanism of the amnestic action of Mz is connected with the cerebral cholinergic neurotransmission. The results of the experiments using Opto-Varimex and Automex equipment for testing the effects of Mz, Mf, Anc and Eucl, and of the combination of Mz with the nootropic agents studied, on the spontaneous motor activity of the experimental rats, lead to the most general conclusion that Mz impedes the development of habituation, considered as a specific type of learning and memory process. To one degree or another, Mf, Anc and Eucl cancel this effect of Mz.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of the nootropic agents adafenoxate and meclofenoxate on brain biogenic monoamines in aged rats.

The effect of the nootropic agents meclofenoxate (Mf) and adafenoxate (Adf) on the content of biogenic monoamines in the frontal cerebral cortex, striatum, hypothalamus, and hippocampus of 22-month-old rats was studied. Mf and Adf were administered orally for seven days twice daily in a dose of 50 mg/kg weight. Both agents tested increased the content of serotonin (5-HT) in the cortex and striatum. Adf also raised the noradrenaline (NA) content in the cortex and hippocampus, lowering the dopamine (DA) level in the striatum. Comparison of the results obtained in the present study with the finding of earlier experiments of ours on 4-5-month-old rats revealed the following: 1. Biogenic monoamines (BMA) in the brain tend to decrease with ageing. 2. In addition to the unidirectional effects of Mf and Adf on the BMA content in the brain of both young and old rats, but in some cases there were also differences. 3. The comparison of the effects of Mf and Adf on the BMA content in the different brain regions with the changes in this content, characteristic of certain diseases, reveals prospects for selectivity in the application of these nootropic agents, which are generally rather similar in pharmacological characteristics.

Aging↗
PubMed1988

Comparative studies on the effects of the nootropic drugs adafenoxate, meclofenoxate and piracetam, and of citicholine on scopolamine-impaired memory, exploratory behavior and physical capabilities (experiments on rats and mice).

The effects of adafenoxate (Adf), meclofenoxate (Mf), piracetam (Pc), and citicholine (CCh) on scopolamine (Scop)--impaired memory and exploratory behavior (experiments on rats) and on physical capabilities (experiments on mice) were studied. In the experiments with scopolamine (2 mg/kg i.p.) we used the step-through passive avoidance method to determine the memory changes. In the case of single treatment with the drugs tested scopolamine was injected immediately after training and Adf, Mf, and CCh at doses of 20 and 100 mg/kg and Pc at a dose of 100 mg/kg were administered immediately after scopolamine. In the case of multiple administration the drugs were applied at the same doses for 7 days before training. Scopolamine was injected immediately after training. Retention tests were given 3 and 24 hours later. All the four drugs tested prevented to a large extent or completely the scopolamine-induced retrograde amnesia. However, significant quantitative differences in the antiamnestic effects of the drugs tested were observed. The effects of the four drugs on exploratory behavior were tested in the Opto Varimex apparatus. After 7-day treatment with the drugs at the doses utilized, the behavior of experimental animals was observed for 10 min, checking out the changes in the frequency of rearing, ambulation, and rotation. Only Adf at a dose of 50 mg/kg significantly decreased rearing and ambulation frequencies; this effect was considered to be an expression of accelerated habituation. The physical capabilities of mice were studied, using the method of treadmill (revolving drum activity cage) training. Before the experiment the mice received orally Adf, Mf, and Pc at a dose of 100 mg/kg or were injected intraperitoneally with CCh at doses of 50 and 100 mg/kg once daily for 7 days. The number of revolutions of the drum cages was counted for 4 hours. Only Pc significantly increased the physical capabilities of mice and much delayed the occurrence of fatigue.

Animals↗
PubMed1988

Comparative studies on the central effects of the angiotensin II analogue (Sar1 azaVal3 Ile8) AT II.

The effects of the newly-synthesized AT II analogue (Sar1 azaVal3 Ile8) AT II were investigated in comparison with the octapeptide AT II and the analogue saralazin (Sar1 Ala8) AT II, using intracerebroventricular administration, with respect to the following parameters: the level of biogenic monoamines (DA, NA and 5-HT) and the metabolites HVA and 5-HIAA in mouse forebrain; the behaviour of the animals--cataleptogenic actions of mice, PTZ convulsive--seizure threshold in mice, apomorphine stereotypy in rats and behaviour of rats in a conflict situation. The analogue (Sar1 azaVal3 Ile8) AT II, unlike saralazin and AT II, was found to induce a rise in the NA and 5-HT levels, causing also catalepsy that is different from the catalepsy induced by saralazine, AT II and haloperidol, because of its rapid onset and decline; it increases the PTZ convulsive--seizure threshold and reduces the number of punished responses to the conflict drinking test (anxiomimetic effect) in a dose 20 times lower than the dose inducing the remaining effects. This effect was antagonized by saralazine. It is concluded that the newly-synthesized analogue (Sar1 azaVal3 Ile8) AT II induces effects similar to those caused by AT II, being at the same time different to a certain extent from the effects (quantitative and qualitative) of octapeptide AT II.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1987

Age-related changes in brain biogenic monoamines and monoamine oxidase.

In experiments on 2-, 10- and 22-month old rats, it was found that essential age-related changes occurred in the brain level of biogenic monoamines (BMA) and in the monoamine oxidase (MAO) activity. In 22-month old rats the levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) markedly declined in most of the brain structures studied. 5-HT significantly decreased in the frontal cortex, striatum and hypothalamus. DA decreased in the cerebral cortex and striatum and NA in the cerebral cortex. However, the NA level in the striatum of 22-month old rats was increased as compared to that in 2-month old rats. In most cases we observed significant differences (a decrease mainly) also in the level of BMA in 22-month old rats as compared to 10-month old rats. The differences, if any, in the BMA levels between 10- and 2-month old rats were less pronounced. The level of 5-hydroxyindole acetic acid (5-HIAA) in the cerebral cortex and striatum of 22-month old rats was significantly higher as compared to that in 2-month old rats. The MAO-T and MAO-A activities in the brain structures studied were significantly higher in 22-month old rats as compared to those in 2-month old rats. The possibility that the age-related changes in brain neurotransmission might be an important element in the neurochemical basis of some behavioral changes in advanced age is considered.

Age Factors↗
PubMed1987

Effects of standardized ginseng extract on learning, memory and physical capabilities.

Standardized ginseng extract (G115, Pharmaton, Lugano) was administered orally at doses of 3, 10, 30, 100 and 300 mg/kg for 10 days as ten rats were used with each dose. With the "shuttle-box" method for active avoidance most pronounced effect on learning and memory was obtained by the dose of 10 mg/kg. With the "step-down" method for passive avoidance the dose of 30 mg/kg significantly improved retention. In the staircase maze training with positive (alimentary) reinforcement only the dose of 10 mg/kg significantly improved learning and memory. The dose of 100 mg/kg greatly increased the locomotor activity of mice. The results show that ginseng at appropriate doses improves learning, memory and physical capabilities. Bell-shaped dose-effect curves, reported with other nootropic drugs, were obtained.

Animals↗
PubMed1987

A study of nootropic drugs for anti-anxiety action.

The effects of adafenoxate (100 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg), piracetam (250 mg/kg), and standardized ginseng extract-G115 (100 mg/kg) applied for five days were studied with Vogel's conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results showed a significant anti-anxiety effect (increases in licking) with adafenoxate and meclofenoxate. Piracetam significantly suppressed licking behaviour and this effect was evaluated as anxiogenic (resulting from the non-specific stimulant action of the drug). Adafenoxate was found to increase also the number of entries into and escapes from the dark compartment without punishment responding. This effect of adafenoxate was considered to be an expression of facilitated conditioned-reflex activity. A beneficial role for the observed anti-anxiety effects of adafenoxate and meclofenoxate in the nootropic action of these drugs is suggested.

Animals↗
PubMed1987

Changes in the 5-HT-binding sites in the cerebral cortex, striatum and hypothalamus of rats during ageing and under the effect of dopaminergic agents.

The changes in the 5-HT1-binding sites, developing during ageing and under the effect of 10-day administration of L-DOPA and haloperidol, were studied in the cerebral cortex, striatum and hypothalamus of 2-, 10- and 22-month-old rats. The values of Bmax of the 5-HT1-binding sites decreased in all three brain structures studied with the ageing of the experimental animals. Both L-DOPA and haloperidol did not change the general character of the changes in the number of 5-HT1-receptors, developing during ageing, but at the same time L-DOPA reduced their density in the three age periods and in the three cerebral areas studied, while haloperidol increased their number in the 2- and 10-month-old rats. The Kd-values of the 5-HT1-receptors manifested very varied changes, determined both by ageing and by the administration of L-DOPA and haloperidol. The generalized interpretation of these results with the results obtained in earlier studies on the age-determined changes in DA2 and the enkephalin receptors, as well as of the content of biogenic monoamines and MAO-activities, made it possible to see new elements in the adaptive possibilities of the cerebral receptors. On the other hand, the results obtained in the present and earlier studies show that ageing is paralleled by deviations in the equilibrium of the cerebral transmitter systems which seem to play an important role for the development of the behavioural changes connected with ageing.

Aging↗
PubMed1987

Effects of the nootropic agents adafenoxate, meclofenoxate and the acetylcholine precursor citicholine on the brain muscarinic receptors (experiments on rats).

The effect of adafenoxate (Af), meclofenoxate (Mf) and citicholine on the brain muscarinic receptors was studied in groups of ten male Wistar rats. The compounds were administered in doses of 50 mg/kg body weight twice daily for 7 days. One hour after the last treatment the animals were killed and the frontal cerebral cortex striatum, the hypothalamus and the hippocampus were removed immediately. Af and Mf were found to diminish significantly and to an analogous extent the density (Bmax) of the muscarinic receptors in the cerebral cortex, striatum and the hippocampus. At the same time, however, the greater decrease of Kd induced by these two nootropic agents, i.e. the increased affinity of the muscarinic binding sites, exceeded considerably the decreased number of the binding sites. These differences in the effects on Bmax and Kd suggest that the functional capacity of the cerebral cholinergic system increases under the action of Mf and Af. The surprising increase in the number of muscarinic receptors in the striatum, observed in citicholine-treated animals, is assumed to be due to the great increase of the dopamine content in this structure, induced by this acetylcholine precursor, observed in other experiments. This increase would result in reduced acetylcholine production by the inhibited cholinergic neurones, with a subsequent increase in the number of the muscarinic receptors.

Acetylcholine↗
PubMed1987

Individually-determined differences in the effects of psychotropic drugs on memory (experiments on rats).

Using the methods for "staircase-maze" training with positive (alimentary) reinforcement and "steps down" passive avoidance with punishment (electroshock) reinforcement, we divided the experimental animals into three groups: "good", "intermediate", and "poor" learners. In the course of seven days the animals of the three groups were treated with five substances and were then tested for retention with both methods. Amphetamine at single doses of 0.1 and 0.5 mg/kg was injected s. c. 30 min before the retention test given on the 7th day after the end of training. The other four drugs were administered twice daily throughout the period between the end of training and retention testing (seven days). Adafenoxate was applied at a dose of 10 mg/kg, piracetam at doses of 50, 150, and 300 mg/kg, and aniracetam at doses of 50 and 150 mg/kg--all the three drugs were administered orally; citicholine was injected at doses of 10 and 50 mg/kg i. p. The effects of the substances tested significantly differed depending on the animal's belonging to one or another group. Furthermore, depending on the retention test, the drug tested and the dose used, we observed differences in the effects not only in the different groups but also in one and the same group. Not taking into account the individual capabilities of experimental animals to acquire a retention task might lead to an incorrect characterization of such an important property of psychotropic drugs as their effect on memory process.

Amphetamine↗
PubMed1987

Effects of meclofenoxate and citicholine on learning and memory in aged rats.

The maze method for active avoidance with punishment reinforcement and the step-through method for passive avoidance with negative reinforcement were used to study the processes of learning and memory in 22-month-old rats, as well as the effects of meclofenoxate (Mf) and citicholine (CCh) on these processes. Meclofenoxate, administered in a dose of 50 mg/kg twice daily for 7 days using the maze-training method, increased the number of responses to the conditioned stimulus, when retention tests were made 24 hours and 7 days after training, whereas citicholine, applied in the same way in a dose of 10 mg/kg, shortened the latency of the responses with reinforcement during the training and increased the number of correct responses to the conditioned stimulus in retention tests 7 days after the training. With the same pattern of administration, both Mf and CCh strongly prolonged the time spent by the animals in the light chamber (i.e., improved retention) in tests using the step-through method 24 hours and 7 days after the training. Both drugs prevented the occurrence of scopolamine-induced (2 mg/kg i.p.) amnesia. A comparison of the results obtained for 22-month-old rats with the results obtained in earlier experiments on 5-month-old rats under fully identical experimental conditions showed that the age-dependent differences in the memory process and in the effects on it of the psychotropic agents meclofenoxate and citicholine were not unidirectional in character.

Aging↗
PubMed1987

Effect of meclofenoxate on pentylenetetrazol kindling in albino rats.

The effects of a single and 5-day treatment of male albino rats with meclofenoxate in a dose of 100 mg/kg on the clonic-tonic convulsions during the kindling phenomenon, induced by multiple injection of a subconvulsive dose (40 mg/kg) pentylenetetrazol (PTZ) were tested. Its effects on convulsions, induced by a single convulsive dose of 100 mg/kg, were investigated for the sake of comparison. Meclofenoxate, introduced in a single dose of 100 mg/kg, lowered the intensity of the convulsions in PTZ-kindled rats. Meclofenoxate treatment for 5 days had an even more pronounced inhibitory effect on PTZ kindling. As regards the convulsions induced by a single injection of a convulsive PTZ dose, meclofenoxate only tends to decrease the percentage of rats with tonic convulsion and the lethality. On the basis of the results of earlier studies, the role of the serotoninergic neurotransmitter system for the observed inhibitory effect of meclofenoxate on PTZ kindling in albino rats is discussed.

Animals↗
PubMed1987

Effects of (D-Ala2,D-Leu5)enkephalinamide on isolated longitudinal muscle guinea pig and rat intestines.

The effects of (D-Ala2,D-Leu5)enkephalinamide, a synthetic analogue of (Leu5) enkephalin, on the contractile activity of isolated segments from guinea-pig and rat colon and rectum were investigated and compared to the effects of natural (Leu5)enkephalin. It was found that the contractile effects of (D-Ala2,D-Leu5)enkephalinamide vary between species and according to the route of administration (application of single doses of cumulative application). (D-Ala2,D-Leu5)enkephalinamide was more potent than (Leu5)enkephalin. It is suggested that in the separate regions of the guinea-pig and rat intestines (D-Ala2,D-Leu5)enkephalinamide activates the same opiate receptors as (Leu5)enkephalin. The higher potency of (D-Ala2,D-Leu5)enkephalinamide could be due to its retarded enzyme degradation because of the replacement of Gly2 by D-Ala and of Leu5 by D-Leu. A selective activation of delta type opiate receptors by (D-Ala2, D-Leu5)enkephalinamide is also assumed.

Animals↗