Centrophenoxine Research Articles

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15–47 ng mL−1, whereas the linearity was assessed to be in the range of 50–2000 ng mL−1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

The Effect of Meclofenoxate on the Transcriptome of Aging Brain of Nothobranchius guentheri Annual Killifish.

Annual fish of the genus Nothobranchius are promising models for aging research. Nothobranchius reproduces typical aspects of vertebrate aging, including hallmarks of brain aging. Meclofenoxate (MF) is a well-known compound that can enhance cognitive performance. The drug is prescribed for asthenic conditions, trauma, and vascular diseases of the brain. It is believed that MF is able to delay age-dependent changes in the human brain. However, until now, there has been no study of the MF effect on the brain transcriptome. In the present work, we performed an RNA-Seq study of brain tissues from aged Nothobranchius guentheri, which were almost lifetime administered with MF, as well as young and aged control fish. As expected, in response to MF, we revealed significant overexpression of neuron-specific genes including genes involved in synaptic activity and plasticity, neurotransmitter secretion, and neuron projection. The effect was more pronounced in female fish. In this aspect, MF alleviated age-dependent decreased expression of genes involved in neuronal activity. In both treated and untreated animals, we observed strong aging-associated overexpression of immune and inflammatory response genes. MF treatment did not prevent this effect, and moreover, some of these genes tended to be slightly upregulated under MF treatment. Additionally, we noticed upregulation of some genes associated with aging and cellular senescence, including isoforms of putative vascular cell adhesion molecule 1 (VCAM1), protein O-GlcNAcase (OGA), protein kinase C alpha type (KPCA), prolow-density lipoprotein receptor-related protein 1 (LRP1). Noteworthy, MF treatment was also associated with the elevated transcription of transposons, which are highly abundant in the N. guentheri genome. In conclusion, MF compensates for the age-dependent downregulation of neuronal activity genes, but its effect on aging brain transcriptome still cannot be considered unambiguously positive.

Biolistic transformation of wheat with centrophenoxine as a synthetic auxin.

Cereal crops, including bread wheat (Triticum aestivum L.), are an important staple food worldwide. With a growing global population, it is evident that current crop production will not meet the rising demands being placed on modern agriculture. Efforts to improve crop yield and stress-tolerance by traditional breeding are labor intensive, time consuming, and highly dependent upon the ability to capture existing and novel genetic variation from a restricted genetic pool. Genetic engineering of crop species is one of several alternatives to traditional breeding for the introduction of novel genetic variation. This recently established technology has proved useful for the introduction of novel traits like pest resistance and herbicide tolerance. As a universal tool for genetic transformation, the Biolistic Gene Gun allows for the genomic integration of novel gene sequences from various sources into a whole host of living organisms.In this chapter, we present a novel and detailed protocol for the Biolistic Transformation of bread wheat that uses the pharmaceutical compound, Centrophenoxine (CPX). The application of CPX as the main auxin-like plant growth regulator in cereal genetic transformation replaces the potent but more toxic herbicide 2,4-D.

Determination of Meclofenoxate Hydrochloride by Resonance Rayleigh Scattering Method Coupled with Flow Injection Technique

In pH 1.0 acidic medium, 12-Tungstophosphoric acid (TP) reacted with meclofenoxate (MFX) to form an ion-associate complex, which resulted in a significant enhancement of the resonance Rayleigh scattering (RRS) intensity. The RRS intensity at the maximum scattering peak of 374 nm was linear to the concentration of MFX in the range of 0.2–12.0 μg mL−1. Therefore, a novel method for the determination of MFX by RRS method coupled with flow injection analysis (FIA) technique was developed. The method has highly sensitivity and the detection limit (3σ) was 5.6 ng mL−1. The present method was applied to the determination of MFX in pharmaceutical preparations and the results agreed well with those provided by the pharmacopeia. The average recovery of standard addition in capsules was 97.0–103.1%. The proposed method exhibited the satisfactory reproducibility with a relative standard derivation (R.S.D.) of 3.7% for 9 successive determinations of 4.0 μg mL−1 MFX. The maximal sample throughput in the optimized system was 48 h−1. In addition, the optimum experiment condition, the effect of coexisting substance, and influence of FIA variables were investigated in the paper.

Effect of centrophenoxine against rotenone-induced oxidative stress in an animal model of Parkinson's disease

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD). The important biochemical features of PD, being profound deficit in dopamine (DA) content, reduced glutathione (GSH), and enhanced lipid peroxidation (LPO) in dopaminergic (DA-ergic) neurons resulting in oxidative stress, mitochondrial dysfunction and apoptosis. Rotenone-induced neurotoxicity is a well acknowledged preclinical model for studying PD in rodents as it produces selective DA-ergic neuronal degeneration. In our previous study, we have shown that chronic administration of rotenone to rats is able to produce motor dysfunction, which increases progressively with rotenone treatment and centrophenoxine (CPH) co-treatment is able to attenuate these motor defects. The present study was carried out to evaluate the antioxidant potential of CPH against rotenone-induced oxidative stress. Chronic administration of rotenone to SD rats resulted in marked oxidative damage in the midbrain region compared to other regions of the brain and CPH co-treatment successfully attenuated most of these changes. CPH significantly attenuated rotenone-induced depletion in DA, GSH and increase in LPO levels. In addition, the drug prevented the increase in nitric oxide (NO) and citrulline levels and also enhanced the activity of catalase and superoxide dismutase (SOD). Histological analysis carried out using hematoxylin and eosin staining has indicated severe damage to mid brain in comparison to cortex and cerebellum and this damage is attenuated by CPH co-treatment. Our results strongly indicate the possible therapeutic potential of centrophenoxine as an antioxidant in Parkinson's disease and other movement disorders where oxidative stress is a key player in the disease process.

Biochemical alterations in rat brain following aluminum exposure: Protection with centrophenoxine

Aluminum (Al) is a neurotoxicant potentially affecting ionic, cholinergic, and dopaminergic neurotransmission in the central nervous system. These alterations are known to be associated with learning ability, adaptive responses, and other aspects of behavior. The present experiment was designed to study the neurotoxic consequences of Al exposure on neurotransmitters like dopamine (DA), serotonin (5-HT), norepinephrine (NE) along with the activity of acetylcholinesterase (AChE). Furthermore, Centrophenoxine (CpH) was administered as a post treatment to evaluate its potential in Al-induced neurotoxicity. The cognitive functions and memory loss were also studied after both Al and CpH administration. Al was administered orally at a dose of 40 mg kg−1 day−1 for a period of 8 weeks, whereas CpH was administered intraperitoneally at a dose of 100−1 mg kg−1 day−1 for a period of 6 weeks. The study was carried out in four regions of the brain, namely cerebrum, cerebellum, medulla oblongata, and hypothalamus. A significant reduction in AChE activity and different neurotransmitters was observed after Al exposure in the regions. CpH as a post treatment proved beneficial in restoring these alterations. Al exposure also affected the cognitive functions and short-term memory, which were significantly improved following CpH post treatment.

An adjunctive preventive treatment for heart disease and a set of diagnostic tests to detect it: Insulin-like growth factor-1 deficiency and cell membrane pathology are an inevitable cause of heart disease

Coronary heart disease (CHD) is a preventable disease with high morbidity and mortality. Largely omitted from the efforts at detection and treatment are the contributions of the lungs, the skeletal muscles and the arteries to heart disease pathology. Also omitted are the effects of the age-related decline in insulin-like growth factor-1 (IGF-1) and the age-related increase in cell membrane pathology. The hypothesis on which this model is based postulates that growing older, over time, necessarily results in pathological changes in the heart, the lungs, the skeletal muscles and the arteries. Additionally, the age-related decline in (IGF-1) that occurs in the otherwise healthy aged population also causes similar pathological changes. The drug portion of the proposed treatment includes the use of the drug acetyl-l-carnitine (ALC) to increase the age-related decreased IGF-1 levels. The drug centrophenoxine (CPH) is used to reverse the age-related pathological changes that inevitably occur in the heart, the lungs, the skeletal muscles and the arteries. A testing procedure is included to improve the detection of heart disease and to monitor the results. It consists of five tests: the monitoring of plasma IGF-1 levels; the monitoring of blood pressure, and in particular elevated systolic blood pressure; the monitoring of blood pressure variability over time; a heart rate recovery time test and a heart rate reserve test. Heart rate reserve is defined as the difference between maximal heart rate and resting heart rate, after treadmill exercise. The changes in test results noted during treatment are an indicator of progress or deterioration in the prevention of heart disease, whatever the case may be.

Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.

Distress and senescence, their reciprocal aggravating-quickening connections, and their related pathologies have a large worldwide impact on healthcare systems in this new millennium. For this reason, Antagonic-Stress (AS)--an advanced integrative therapy, with specific synergistic composition, and patented internationally--represents a significant strategy in health, aging, and longevity. Clinical research with AS proves the drug's efficacy in the management of distress (neurotic, stress-related, and affective disorders; behavioral syndromes associated with physiological disturbances and physical factors; mental and behavioral disorders due to psychoactive substance uses) and psychogeriatrics [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial psychopathological instruments and psychometric tests in multiple assessments used for gerontopsychiatry demonstrated strong improvements after AS administration in early-moderate stages of Alzheimer or vascular dementia, as well as in other OMD. In addition, comparative clinical studies evinced the superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These comparative clinical trials agreed closely with comparative preclinical research and confirmed AS synergistic homeostatic, adaptogenic, antioxidative, cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective actions against oxidative stress recommend this orthomolecular therapy in stress, aging, and free radical pathology.

Pharmacological interventions against aging through the cell plasma membrane: a review of the experimental results obtained in animals and humans.

As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187-199, 2001), oxyradicals cannot be considered only as harmful by-products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site-specific, radical-induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH(*) free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane-related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE-001 is also reported.

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 peroxidein vivohas 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−1body wt. alone or with either EGb at a dose of 150 mg kg−1body wt. or Zn at 10.5 mg kg−1body 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.

Antagonic-stress superiority versus meclofenoxate in gerontopsychiatry (alzheimer type dementia)

A double blind, comparative, parallel and randomized clinical trial was used for evaluation of two nootropics with anti-aging actions: Meclofenoxate (MF) and Antagonic-Stress (AS). Sixty-three old persons divided into 2 groups (average age: 68.6 and 70.8 years, respectively) with senile dementia of Alzheimer type (SDAT), of mild to moderate intensity (criteria of DSM-III-R, APA, 1987; and ICD-10, WHO, 1990) were treated with one of these nootropica. Baseline and final psychogeriatric symptomatology after three months of treatments were multiply assessed: psychogeriatric by Sandoz Clinical Assessment-Geriatric scale, Self-Assessment Scale-Geriatric and their subscales; psychometric by Wechsler Memory Scale and Wechsler Adult Intelligence Scale. Prolonged treatments with MF and AS significantly decreased the psychogeriatric scores in scales and subscales, improved the cognitive performance (attention, concentration, memory, performance IQ, full IQ) and diminshed the deterioration index (ANOVA). Therapeutical effects of AS (a neurometabolic complex containing MF) were significantly superior against MF alone (ANCOVA). MF and AS actions are discussed in connection with the brain cholinergic system, lipid peroxidation and free radical scavengers, deceleration of the aging rate, brain and erythrocyte lipofuscinolysis, multiple anti-oxidant formula, multivitamin and multimineral supplementation and with the superiority of multitherapy versus monotherapy in senile dementia and for improving the IQ and the maladaptative behavior.

Effects of centrophenoxine on body composition and some biochemical parameters of demented elderly people as revealed in a double-blind clinical trial

A double-blind clinical trial was performed on 50 persons (25 men, 25 women, average age 77 years) suffering from dementias of medium level (DSM III, Category 1, ICD No. 299). All subjects were residents in an old age home. The patients were treated first for 2 weeks by placebo tablets. During this period, body composition parameters were determined and these data served as controls. This was then followed by an 8-week-long treatment with the nootropic drug, centrophenoxine (CPH), 2 g/day distributed in 2×2 tablets of Helfergin 500 (Promonta, Hamburg, F.R.G.), or placebo tablets of identical size. After 8 weeks the laboratory tests were repeated again. The randomization code for verum or placebo treatment was revealed only after completing the trial. Four dropouts occurred during the treatment period. The total body water, extracellular water volume and exchangable Na + were determined by means of radioisotope methods. Plasma volume (PV) was measured by indocyanine-green dilution test. Body weights were also recorded. From the above data further parameters could be calculated. Serum lipid data as well as several hormone levels were also checked in the blood samples. The main results were better performance in psychometric tests (Pék et al., 1989) and a significant increase of the average intracellular water content (2.2–2.5% by weight) in the verum-treated group. The rehydration of the intracellular mass due to CPH treatment is consistent with the OH •. free radical scavenger properties of CPH and the predictions of the membrane hypothesis of aging.

On the role of intracellular physicochemistry in quantitative gene expression during aging and the effect of centrophenoxine. A review

The turnover of proteins in biological systems is due mostly to an ever-occuring damaging (cross-linking) effect of the OH' free radicals. The replacement of the damaged proteins requires a continuous gene expression. A key issue of experimental gerontology is why the gene expression maintains the fidelity but loses the speed during aging. The membrane hypothesis of aging (MHA) proposes a cellular mechanism based on the fact that the more compact cellular structures (e.g., membranes) are damaged faster than the more diluted ones (e.g., cytosol). In addition, the cell membrane is exposed also to the residual heat-induced damage deriving from a frequent discharge of its electric polarity. Therefore, one can assume that even an extremely small incompleteness of the replacement of the damaged membrane components per turnover cycle may result in an error accumulation, which may be responsible first for the inhibition of growth, then for aging of cells. In agreement with this hypothesis, neurons display a life-long, gradual loss of the passive potassium permeability of the cell membrane, resulting in a continuous dehydration of the intracellular mass, i.e., an increase of physical density. Theory and experimental models show that this latter process causes a slowing down of all enzyme functions including those realizing the gene expression and the elimination of the damaged components. Increase of-the dry mass content of cells and tissues is an obligatory process for maturation; however, later on it leads to aging. The known nootropic effects of centrophenoxine (CPH) can be interpreted on the basis of the OH' radical scavenger properties of dimethylaminoethanol (DMAE) which is incorporated in the neuronal membranes of the brain in form of phosphatidyl-DMAE. The protective effects of CPH (and of similar, newly synthesized other drugs) on the membrane components can slow down the age-dependent deteriorations of the intracellular physicochemistry, in agreement with the predictions of the MHA.

Gerontopsychological studies using NAI (‘Nürnberger Alters-Inventar’) on patients with organic psychosyndrome (DSM III, Category 1) treated with centrophenoxine in a double blind, comparative, randomized clinical trial

A double blind clinical trial was performed on 50 persons (25 men, 25 women) over the age 60 (average age: 77 years). They suffered from dementias of medium level (DSM III, Category 1, ICD No. 299), and had been residents in an old age home longer than 3 months at the start of the trial. The patients were treated first for 2 weeks by placebo tablets and their initial performance was recorded during this period by using the Nuremberg Gerontopsychological Inventory (NAI). This was then followed by a treatment for 8 weeks with the nootropic drug, centrophenoxine (CPH), the dose of which was 2 g/day distributed in 2 x 2 tablets of Helfergin 500 (Promonta, Hamburg, FRG), or with placebo tablets of identical size, then the NAI test was repeated again. Verum or placebo treatment was selected randomly and the code was revealed only after having elaborated all the results of the trial. During the treatment period four drop-outs occurred for intercurrent diseases. Evaluation was based on a semi-quantitative, intra-individual comparison of the performance before and after treatment. The results obtained suggest that CPH treatment may be useful in dementias of medium level in quite old groups of patients, since 48% of the verum group displayed improvements in the memory functions against 28% of the placebo group. CPH seems to be a useful and harmless drug in the treatment and most probably also in prevention of the dementias.

Ultrastructural analysis of the action of meclofenoxate on retrovirus-transformed cells

The ultrastructure of hybridoma cells cultured with 5.10(-4) centrophenoxine (CP) has been studied. It is shown that CP effects hybridomas and prevents retrovirus exocytosis. The effect of CP on Ca-calmodulin system associated with cytoskeleton is suggested.

Superoxide radical scavenging ability of centrophenoxine and its salt dependence in vitro

The superoxide radical scavenging ability of centrophenoxine (CPH) and its components (dimethylaminoethanol = DMAE, p-chlorophenoxyacetic acid = PCPA) was studied in vitro using the method of pyrogallol autoxidation, cytochrome c reduction and photoxidation of o-dianisidine in salt free assay media and in the presence of increasing NaCl or KCl concentrations. The CPH proved to be a superoxide radical scavenger in all three systems used, however, the rate constant for this reaction was rather low (1.7 × 10 2 M −1 s −1). This scavenging ability decreased linearly with increasing ionic strength. DMAE and PCPA behaved in a somewhat contradictory manner. The former proved to be a weak superoxide radical generating compound being partially sensitive to the ionic strength. The latter showed either superoxide radical scavenging or generating effects on various assays depending on the actual salt concentrations of the media. On the basis of the results one has to assume that the superoxide radical scavenger ability of CPH may hardly be responsible for the in vivo effects of this compound, therefore, its OH· radical scavenger reactions the rate constant of which is about 10 9 M −1 s −1 (See Ref. 28.) may be of much greater importance.

Superoxide radical scavenging ability of centrophenoxine and its salt dependence in vitro

The superoxide radical scavenging ability of centrophenoxine (CPH) and its components (dimethylaminoethanol = DMAE, p -chlorophenoxyacetic acid = PCPA) was studied in vitro using the method of pyrogallol autoxidation, cytochrome c reduction and photoxidation of o -dianisidine in salt free assay media and in the presence of increasing NaCl or KCl concentrations. The CPH proved to be a superoxide radical scavenger in all three systems used, however, the rate constant for this reaction was rather low (1.7 × 10 2 M −1 s −1 ). This scavenging ability decreased linearly with increasing ionic strength. DMAE and PCPA behaved in a somewhat contradictory manner. The former proved to be a weak superoxide radical generating compound being partially sensitive to the ionic strength. The latter showed either superoxide radical scavenging or generating effects on various assays depending on the actual salt concentrations of the media. On the basis of the results one has to assume that the superoxide radical scavenger ability of CPH may hardly be responsible for the in vivo effects of this compound, therefore, its OH· radical scavenger reactions the rate constant of which is about 10 9 M −1 s −1 (See Ref. 28.) may be of much greater importance.

Electron spin resonance spectroscopic demonstration of the hydroxyl free radical scavenger properties of dimethylaminoethanol in spin trapping experiments confirming the molecular basis for the biological effects of centrophenoxine

The ADP-Fe(II)-H 2O 2 system generates OH free radicals which can be trapped by 5,5-dimethyl-1-pyrroline- N-oxide (DMPO) thus yielding a measurable signal by electron spin resonance spectroscopy. The amount of DMPO-OH spin adduct formed under certain conditions decreased considerably, if dimethylaminoethanol (DMAE), p-chlorophenoxyacetic acid (PCPA) or centrophenoxine (CPH) were present in comparable concentrations to that of DMPO. It has been demonstrated that such an effect cannot be attributed to any interference of the tested compounds with the Fe(II) and its oxidability by H 2O 2. The reaction of DMAE with OH free radicals was demonstrated also by using other spin traps. These spin traps reacted with OH free radicals either not at all (phenyl-tert-butylnitrone, PBN) or only to a slight extent (alfa-pyridyl-1-oxide- N-tert-butylnitrone, 4-POBN). DMAE was also a competitive OH free radical scavenger with proline and hydroxyproline, both of which have recently been shown to react with OH free radicals to form nitroxyl free radicals. On the basis of the experimental results, the OH free radical scavenger property of DMAE can be regarded as firmly established. This result supports the molecular mechanism proposed for the explanation of the anti-aging effects of CPH in terms of the membrane hypothesis of aging.

The influence of centrophenoxine hydrochloride on SSEP in apallic patients

The influence of centrophenoxine hydrochloride on SSEP in apallic patients

Alterations of the synaptosomal membrane ‘microviscosity’ in the brain cortex of rats during aging and centrophenoxine treatment

Synaptosomal and myelin fractions were isolated from the brain cortex of young, adult and old male CFY rats (2, 12 and 24 mth, respectively). The purity of the fractions was tested by transmission electron microscopy and marker enzyme assays. The cholesterol content of the fractions was also determined. Samples of the fractions were labelled with diphenylhexatriene (DPH) and the fluorescence anisotropy ( r) of the label was measured at various optical densities. The values of r extrapolated to zero optical density were compared in the age groups and used for calculating the ‘microviscosity’ of the membranes. The ‘microviscosity’ of synaptosomal membranes displayed a significant age-dependent increase: from 2.3±0.02 (SD) in the young group it increased to 2.6±0.03 poise by the age of 24 mth at 37°C. Most of this increase occurred between the adult and old age. The cholesterol content of the synaptosomes also increased significantly during aging. Centrophenoxine (CPH)-treatment with 100 mg/kg body weight daily dose for 2 mth was able to reverse the age-dependent alterations of both the membrane ‘microviscosity’ and the cholesterol content in the synaptosomes: the values returned nearly to the adult level. The results obtained are interpreted in terms of the membrane hypothesis of aging attributing a primary role to the free-radical induced membrane damage in cellular aging.