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At least 19 recordsLinked to original sources

Effects of meclofenoxate on learning and memory--dependence on the experimental conditions.

In experiments on male albino rats, it was found that meclofenoxate at a dose of 100 mg/kg i. p. applied 7 days before and 5 days during shuttle-box training did not influence learning but significantly facilitated retention (retention test was given 7 days after the end of training). With the step-through method for passive avoidance meclofenoxate at the same dose applied for 7 days improved learning and retention. In the staircase maze training with alimentary reinforcement and in the step-down passive avoidance situation, meclofenoxate at a single dose (50 mg/kg i. p.) applied before or immediately after training only tended to facilitate learning and retention, while applied at the same dose twice daily for 5 days, it significantly improved learning and retention. When meclofenoxate at a dose of 50 mg/kg i. p. was administered twice daily for 5 days in parallel with the staircase maze training, learning reached its maximum on the 5th day and remained at this level till the 10th training day even after withdrawal of meclofenoxate. In the control animals the improvement of learning progressively increased till the 10th training day. The present results suggest that the learning- and memory-facilitating effect of meclofenoxate is influenced by the training method, motivation, dose used and treatment duration.

Animals↗

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↗

Effect of the combination of the benzodiazepine tranquilizer medazepam and the nootropic agent meclofenoxate on the activity of rat brain muscarinic receptors.

1. The effect of 7-day treatment with the benzodiazepine tranquilizer medazepam (5 mg/kg), the nootropic agent meclofenoxate (100 mg/kg) and their combination in the same doses on the binding activity of muscarinic receptors in four rat brain structures (cerebral cortex, striatum, hippocampus and hypothalamus) were studied using the antagonist [3H]-1-quinuclidinyl benzylate [( 3H]-QNB) as radio-ligand. 2. Medazepam treatment caused significant decrease of muscarinic receptor binding affinity (Kd) and of the receptor binding capacity (Bmax) in the brain structures studied. The number of muscarinic binding sites was unsignificantly decreased only in the hippocampus. 3. Meclofenoxate treatment caused an increase of muscarinic receptor affinity and a decrease of the binding capacity in the cerebral cortex and hypothalamus and an increase of the binding affinity in the striatum and hippocampus. 4. The combination of medazepam and meclofenoxate caused no significant changes of both muscarinic receptor characteristics in the hippocampus and of the receptor affinity in the striatum and hypothalamus in comparison with control rats. The Bmax values were decreased in the cerebral cortex, striatum and hypothalamus when compared with control animals. The differences observed were slighter than those determined after the comparison of medazepam treated rats with control rats. 5. The results obtained afford an opportunity to suggest that the nootropic agent meclofenoxate acts to moderate the effect of the benzodiazepine tranquilizer medazepam on the activity of rat brain muscarinic receptors.

Animals↗

Quantitative studies of the effects of aging, meclofenoxate, and dihydroergotoxine on intraneuronal lipopigment accumulation in the rat.

Intraneuronal lipopigment accumulation is associated with ageing and certain diseases, and there are many claims that this can be influenced by drugs, particularly meclofenoxate (centrophenoxine). The various unsubstantiated or conflicting reports of the effects of this drug in animal studies indicate the need for methods for the demonstration of lipopigment accumulation in adequately defined, easily-identified, and relatively homogeneous neuronal populations; this study has validated two such methods by demonstrating significant differences between groups of rats at different ages in respect of measured lipopigment autofluorescence intensity from the most heavily pigmented regions of a subpopulation of Purkinje cells, and of the area overlying intraneuronal lipopigment in a region of the hippocampus. These methods were then used to investigate the effects of daily (5 days per week) intraperitoneal injections of meclofenoxate or dihydroergotoxine, over a period of 12 weeks, before sacrifice at 13.5 months. No significant effects of meclofenoxate were detected, but dihydroergotoxine administration was associated with a significant increase in mean area overlying intraneuronal lipopigment in the CA3a region of the hippocampus. The results do not confirm that meclofenoxate can induce a reduction in intraneuronal lipopigment, but suggest that chronic dihydroergotoxine administration was associated with an increase in intraneuronal volume of lipopigment in the cell bodies of CA3a hippocampal neurones.

Aging↗

Effects of meclofenoxate on the level and turnover of biogenic monoamines in the rat brain.

The level and turnover of biogenic monoamines in some rat brain structures were determined after treatment with meclofenoxate at a dose of 50 mg/kg administered i.p. two times a day (9 a.m. and 5 p.m.) for 5 days. Meclofenoxate decreased dopamine (DA) turnover in the frontal cortex and striatum and highly increased it in the hypothalamus. The DA level significantly declined in the striatum, tended to decline in the cortex and significantly rose in the hypothalamus. The noradrenaline (NA) turnover and level in the cortex and striatum were decreased. Meclofenoxate decreased serotonin (5-HT) turnover in the cortex, striatum and hypothalamus and increased it in the pons. At the same time, the 5-HT level rose in the cortex, striatum and pons and declined in the hypothalamus. These results suggest the neurochemical basis of the psychotropic and neuroendocrine effects of meclofenoxate.

Animals↗

[Increase in cell metabolism in normal, diploid human glial cells in stationary cell cultures induced by meclofenoxate].

Quantitative biochemical studies were undertaken in order to examine the influence of the accumulation of lipofuscin in secondary lysosomes on cell metabolic activities of normal diploid human glia cells in a stationary cell culture system. Glia cells accumulate lipofuscin as a function of the duration of the stationary cultivation in vitro. The accumulation of lipofuscin can be decreased by the long-term treatment with the pharmacon meclofenoxate (centrophenoxine, Helfergin). Concomitant with the reduction of the accumulated lipofuscin, meclofenoxate-treated glia cells show enhanced rates of RNA synthesis, protein synthesis and glucose uptake. Most likely, in meclofenoxate-treated normal diploid human glia cells in vitro, the utilisation of glucose is shifted from glycolysis to the pentose phosphate pathway. The data suggest that the meclofenoxate-induced reduction of lipofuscin accumulation has a positive effect on cell metabolic functions and causes a delay of the cellular aging of the human glia cells in vitro.

Diploidy↗

Meclofenoxate therapy in tardive dyskinesia: a preliminary report.

Tardive dyskinesia seems to occur as a result of diminished cholinergic and enhanced dopaminergic activity in the striatum. Meclofenoxate has been shown to increase cerebral cholinergic activity. To ameliorate the tardive dyskinesia, meclofenoxate was given orally, 600-1200 mg/day, for 6-12 weeks. The effects of the drug were evaluated by scoring the degree of involuntary movement. Among 11 subjects with tardive dyskinesia or dystonia, 4 improved markedly, 1 moderately, 2 slightly, and there was no improvement in 4. One patient with subacute oral dyskinesia, induced by administration of neuroleptics for 1 month, improved markedly. The possibility that meclofenoxate may be effective in dealing with dyskinesias that are induced by neuroleptics warrants further attention.

Administration, Oral↗

Increases in choline levels in rat brain elicited by meclofenoxate.

Meclofenoxate, the p-cholorophenoxyacetic acid ester of deanol, was found to dramatically elevate choline (Ch) levels in the rat CNS. In the hippocampus, this elevation in choline was accompanied by a new elevated steady state level in acetylcholine (ACh). No such coupling was observed in the striatum or parietal cortex. Deanol also elevated choline levels in the CNS but was about half as potent as meclofenoxate; p-chlorophenoxyacetic acid was inactive in this respect. Lesions of striatal neurons with kainic acid and of hippocampal cholinergic nerve endings with surgical section of the fimbria indicated that the changes in choline levels were mainly extraneuronal. In spite of the changes in choline and ACh levels, no consistant alterations in ACh turnover were measured. In summary, meclofenoxate induced dramatic alterations in CNS choline metabolism and may, therefore, be a useful therapeutic tool for potentiating depressed cholinergic neurons.

Animals↗

The differential effects of meclofenoxate on memory loss in the elderly.

A double-blind study of the effects of meclofenoxate on memory performance of fit, able, elderly subjects was carried out. A number of performance measures, designed to measure various aspects of memory function were employed. These revealed that meclofenoxate appears to increase the consolidation of new information into long-term memory, but does not affect other aspects of remembering. It was also found that significantly more of the subjects receiving meclofenoxate reported an increased level of mental alertness.

Aged↗

Comparative studies on the influence of ONK (N(5-hydroxynicotinoil) glutamic acid), piracetam and meclofenoxate on the learning- and memory-impairing effect of scopolamine, clonidine, and methergoline.

The effects of the new compound N(5-hydroxynicotinoil)glutamic acid (ONK) in comparison with the well-known nootropic drugs piracetam and meclofenoxate on cognitive functions impaired by scopolamine, clonidine or methergoline were examined in albino rats and mice. The changes in learning and memory were studied by the two-way active avoidance "shuttle-box", passive avoidance "step-down" in rats and passive avoidance "step-through" in mice. The present results showed that ONK (50 mg/kg) injected intraperitoneally (i. p.), piracetam (800 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training completely antagonized the scopolamine-provoked amnesia in step-through-trained mice. ONK (50 mg/kg) administered i. p., piracetam (600 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training abolished the memory-impairing effect of clonidine in shuttle-box-trained rats and the amnestic effect of methergoline in step-down trained rats. The observed antiamnestic effects of the nootropic drugs studied are probably realised through their influence on cholinergic, noradrenergic and serotoninergic neurotransmission. The favourable effect of ONK on cognition might be of interest for therapeutic practice.

Animals↗

Effects of meclofenoxate and Extr. Rhodiolae roseae L. on electroconvulsive shock-impaired learning and memory in rats.

In experiments on albino rats, the authors studied the effects of meclofenoxate and Extr. Rhodiolae roseae on the memory-impairing action of convulsant electroshock. "Step-down" passive avoidance training with negative reinforcement was used to trace the changes in memory. Meclofenoxate administered i.p. in a dose of 100 mg/kg body weight for five days prevented the retrograde amnesia observed after convulsant electroshock upon retention testing on the 3rd and 24th hr after the end of the training session. The Rhodiola extract administered orally in a dose of 0.10 ml/rat for 10 days, which in other experimental approaches improved learning and memory, remained ineffective here. The role of biogenic monoamines in the learning- and memory-improving effects of meclofenoxate is considered on the basis of earlier studies by the authors.

Animals↗

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↗

[The effect of meclofenoxate on the growth, fertility and number of offspring in Wistar rats].

In experiments with rats concerning teratological aspects of meclofenoxate it was demonstrated that this drug reduces the teratogenicity in Wistar rats. Meclofenoxate leads in the fetuses of rats to a significant increase of the weight when the dams were treated prenatally with the ester. Besides, meclofenoxate causes in continuous series of generations an increase of fertility which results in a higher number of offsprings.

Animals↗

Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats).

1. The effects of Adafenoxate (Adf), meclofenoxate (Mf) and citicholine (CCh) administered at a daily dose of 100 mg/kg for 7 days on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cerebral cortex, striatum, hippocampus and hypothalamus of rats were studied. 2. Adafenoxate increased the NA level in the striatum and decreased it in the hypothalamus; it increased the DA level in the cerebral cortex and hypothalamus and decreased it in the striatum; it increased the 5-HT level in the cerebral cortex and decreased it in the hippocampus. 3. Meclofenoxate decreased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the hippocampus and hypothalamus and the 5-HT level in the cerebral cortex, striatum, hippocampus and hypothalamus. 4. Citicholine increased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the striatum and the 5-HT level in the cerebral cortex, striatum and hippocampus. 5. An attempt is made to explain some similarities and differences in the behavioral effects of the drugs tested (and those observed in other studies) by the changes they induce in brain biogenic monoamines.

Animals↗

Kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma.

The kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma have been compared with those of clofibrate. The hydrolysis rate in fractionated plasma was determined in the presence and absence of a plasma esterase inhibitor, tetraethyl pyrophosphate. The kinetic data indicated that clofibrate decomposed only by esterase-induced hydrolysis, which was inhibited by binding of clofibrate to plasma proteins. In contrast to clofibrate, meclofenoxate decomposed rapidly in human plasma via spontaneous hydrolysis as well as esterase-induced hydrolysis. The spontaneous hydrolysis appeared to be inhibited by some components present in the esterase fraction isolated from plasma, while no significant inhibition of the hydrolysis by protein binding was observed.

Blood Proteins↗

Differences between the effects of two meclofenoxate doses on active training for two-way avoidance in rats.

Male Wistar rats were trained for active two-way avoidance in a shuttle-box apparatus for five consecutive days. Meclofenoxate, in doses of 100 and 300 mg/kg i.p., was applied in two separate groups of rats, 60 min before the beginning of the training. Meclofenoxate (Mf), applied in a dose of 100 mg/kg, slightly improved the avoidance training, whereas in a dose of 300 mg/kg it "deteriorated" learning during the last two training days. Retrospective analysis of the experimental results showed that Mf caused a dose-dependent increase in the percentage of rats who were "poor learners", compared with the percentage of "poor learners" among the controls. On the other hand, the Mf-treated "good learners" manifested an essentially better capacity for avoidance training, compared with the control "good learners". The data obtained suggest that Mf increases the adaptational capacities of rats trained for active avoidance possibly in two different ways: in part of the animals it causes improvement of the conditioned reflex activity, in another part of the animals it increases their resistance to the stressogenic stimuli used during such a training.

Animals↗

The effect of meclofenoxate with ginkgo biloba extract or zinc on lipid peroxide, some free radical scavengers and the cardiovascular system of aged rats.

Aged rats are highly prone to many physiological changes such as blood pressure and heart rate. These changes could be due to modification in membrane phospholipid composition of their blood vessels. Lipid peroxide in vivo has been identified as a basic deteriorative reaction in cellular mechanisms of aging in human. The effect of a nootropic drug, meclofenoxate (MF) or its combination with extract of ginkgo biloba (EGb-761) or zinc (Zn) on malondialdehyde (MDA) product as an index of endogenous lipid peroxidation; phospholipid; glutathione (GSH) and protein thiols (PrSHs) contents as well as superoxide dismutase (SOD) activity in blood, brain, heart and liver of 24-month-old male rats was investigated. Aged rats were treated with MF once daily at oral doses of 100 mg kg-1 body wt. alone or with either EGb at a dose of 150 mg kg-1 body wt. or Zn at 10.5 mg kg-1 body wt. for 4 weeks. This study showed that aging caused a higher increment in MDA level of brain and heart than liver and plasma accompanied with reduction in brain and heart phospholipid contents as well as alteration of the antioxidant systems as compared to 4-month-old rats. Treatment of aged rats with MF alone or combined with either EGb or Zn caused improvement in the measured free radical scavengers especially in brain and heart tissues. Our results also showed that both EGb and Zn induced a significant potential effect of MF action on blood pressure and heart rate. The results were explained in the light of the antioxidant properties of EGb and Zn. Thus it is concluded that EGb and Zn have a beneficial role with MF in diminishing cumulative oxidative changes in aging.

Aging↗

Prediction of the stability of meclofenoxate injection in parenteral admixtures.

A new method for predicting pharmaceutical stability in parenteral admixtures was studied using meclofenoxate hydrochloride injection as a model preparation. The pH and temperature of clinical parenteral admixtures are not constant, unlike experimental buffer solutions, and it is impossible to predict the accurate degradation ratio by the preceding method described by many authors. This study provides a solution to this problem making possible the accurate prediction of degradation ratios of pharmaceuticals even in such complicated systems.

Drug Stability↗