In silico and in vivo study of radio-iodinated nefiracetam as a radiotracer for brain imaging in mice

This study presents development and characterization of a radiotracer, [125I]iodonefiracetam ([125I]iodoNEF). Labeling with high yield and radiochemical purity was achieved through the formation of a [125I]iodoNEF radiotracer after investigating many factors like oxidizing agent content (chloramines-T (Ch-T)), substrate amount (Nefiracetam (NEF)), pH of reaction mixture, reaction time and temperature. Nefiracetam (NEF) is known as nootropic agent, acting as N-methyl-d-aspartic acid receptor ligand (NMDA). The radiolabeled compound was stable, and exhibited the logarithm of the partition coefficient (log p) value of [125I]iodonefiracetam as 1.85 (lipophilic). Biodistribution studies in normal mice confirmed the suitability of the [125I]iodoNEF radiotracer as a novel tracer for brain imaging. High uptake of 8.61 ± 0.14 percent injected dose/g organ was observed in mice

A Review of the Actions of D-cycloserine, a Putative Nootropic Agent, at the NMDA Receptor Complex-Associated Glycine Binding Site

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Novel Validated Analytical Method Based on Potentiometric Transduction for the Determination of Citicoline Psychostimulant/Nootropic Agent

Herein, a novel validated potentiometric method is presented for the first time for citicoline determination. The method is based on measuring the potential using new constructed citicoline electrodes. The electrodes are based on the use of citicolinium/phosphomolybdate [Cit]2[PM] (sensor I) and citicolinium/tetraphenylborate [Cit][TPB] (sensor II) ion association complexes. These sensory materials were dispersed in plasticized polyvinyl chloride (PVC) polymeric membranes. The sensors revealed a Nernstian response with the slopes 55.9 ± 1.8(r2 = 0.9994) and 51.8 ± 0.9 (r2 = 0.9991) mV/decade over a linearity range of 6.3 × 10−6–1.0 × 10−3 and 1.0 × 10−5–1.0 × 10−3 M and detection limits of 3.16 × 10−6 and 7.1 × 10−6 M for sensors I and II, respectively. To ensure the existence of monovalent citicoline, all measurements were performed in 50 mM acetate buffer at pH 3.5. All presented electrodes showed good performance characteristics such as rapid response, good selectivity, high potential-stability and long life-span. Method verification and validation in terms of response linearity, quantification limit, accuracy, bias, trueness, robustness, within-day variability and between-days variability were evaluated. The method was introduced for citicoline determination in different pharmaceutical formulations and compared with the standard high performance liquid chromatography (HPLC) method.

Pharmacokinetic properties of an innovative nootropic agent based on a derivative of 3,7-diazabicyclo[3.3.1]nonane

The pharmacokinetics and bioavailability of a derivative of 3,7-diazabicyclo[3.3.1]nonane exhibiting a nootropic effect, were studied after a single dose to rats. The pharmacokinetics of the compound was studied after oral and intravenous administration to 270 male rats Sprague Dawley at doses of 2.5 mg/kg, 13 mg/kg and 25 mg/kg. Its distribution in organs and tissues (brain, thymus, heart, lungs, liver, kidneys, and spleen) was also investigated. It was found that after a single intravenous administration, the investigated substance was determined in the blood of animals for 24 h; the half-life was 4.69 h. The relative bioavailability of the 3,7-diazabicyclo[3.3.1]nonane derivative after oral administration was 42.3%, thus suggesting the prospect of creating dosage forms for oral administration. After a single oral administration, the dose dependence of AUC0-t was exponential. The substance is characterized by heterogeneous distribution in the body with preferential accumulation mainly in well-vascularized tissues.

Unani Perspective and New Researches of Sa’ad ku’fi (Cyperus rotundus): A Review

Cyperus rotundus L. (cyperaceae) is an important medicinal plant which is used in traditional medicine particularly in Unani system of medicine. It is commonly known as motha which is a lawn grass and grows easily in tropical, subtropical and temperate regions. Major Chemical constituents enclosed with this herb are flavonoids, tannins, glycosides, furochromones, monoterpenes, sesquiterpenes, sitosterol, alkaloids, saponins, terpenoids, essential oils, starch, carbohydrates, protein, separated amino acids and many other secondary metabolites. Different parts of cyperus rotundus have been reported to possess multiple pharmacological actions like antibacterial, anticancerous, anticonvulsant, antidiabetic, antidiarrheal, antigenotoxic, anti-inflammatory, antilipidemic, antimalarial, antimutagenic, antiobesity, antioxidant, anti-uropathogenic, hepatoprotective, cardioprotective, neuroprotective, and nootropic agent. Keywords: Unani, sa’ad, flavonoids, sesquiterpenes, antibacterial, antilipidemic.

DOCOSAHEXAENOIC ACID ADMINISTRATION AMELIORATES SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT IN MICE

Objective: The main objective of this work was to study the memory-enhancing activity of docosahexaenoic acid (DHA) supplementation in normal memory function and scopolamine-induced impaired memory in mice.Methods: The gum acacia suspension of DHA was administered by gavage at the dose of 200 and 300 mg/kg in mice for 30 days to evaluate memory-enhancing potential on normal and scopolamine-induced impaired memory in albino mice. Escape latency in Morris water maze (MWM) and transfer latency (TL) in elevated plus maze (EPM) were recorded, respectively. Mice were given four trial sessions per day to locate the platform for 4 days in MWM model. Scopolamine 1 mg/kg was injected i.p. to produce memory impairment in mice.Result: DHA suspension at the dose of 300 mg/kg showed significant reduction of escape latency and TL as compared to control group, and the effect was comparable to that of standard nootropic agent piracetam at the dose of 100 mg/kg in normal and scopolamine-treated mice. However, DHA at the dose of 200 mg/kg showed significant memory-enhancing effect in only scopolamine-induced impaired memory model.Conclusion: The study revealed that the chronic administration of DHA exhibited significant memory-enhancing activity against both normal as well as scopolamine-treated impaired memory mice groups, however, this effect was more marked on scopolamine-induced memory impairment as compared to normal memory function.

Pharmacokinetics of noopept and its active metabolite cycloprolyl glycine in rats

The study of the pharmacokinetics of new drugs and the identification of active metabolites is a necessary step for effective and safe use in the clinical practice. It is especially important for peptide drugs due to their enzymatic instability, low bioavailability and poor permeability through the blood-brain barrier (BBB). The role of endogenous neuropeptides containing cyclic amino acids, proline, pyroglutamic acid, and glycine, in the regulation of memory processes is known as terminal peptide fragments. The development of nootropic drugs based on natural neuropeptides with high pharmacological activity and improved pharmacokinetic properties (enzymatic stability, high bioavailability, and good permeability through the BBB) is an important problem of modern neuropsychopharmacology. Developed drugs – representing short (di- and tri-) peptides appear to meet these requirements. In the Zakusov Research Institute of Pharmacology a nootropic agent noopept (N-phenylacetyl-prolyl-L-glycine ethyl ester), was developed and introduced into medical practice, studies of its pharmacokinetics in ratsrevealed that the noopept metabolite found in the rat plasma and brain, cyclo-prolyl-L-glycine (CPG), differed significantly in its pharmacokinetic parameters from noopept, but at the same time it had similar noopept multi-component spectrum of pharmacological action, namely the influence on higher integrative functions of memory.

Effect of Salacia reticulata W. and Clitoria ternatea L. on the cognitive and behavioral changes in the streptozotocin-induced young diabetic rats

Background:Diabetes mellitus (DM) of juvenile onset affects both the peripheral and central nervous systems (CNS). However, central effects are less documented and studied than peripheral deficits. Currently, the only feasible treatment available for type 1 DM (T1DM) is insulin which has its own limitations. Hence, an alternative therapy, especially a newer herbal formulation is very much the need of the time. The present study aimed to determine the effects of the alcoholic extracts of roots of theMethods:Diabetes was induced in 25-day-old Wistar rats by streptozotocin (50 mg/kg bw, IP). Animals were divided into seven groups (n=6). Rats were treated with root extracts of SR and CT (100 mg/kg BW each) for 30 days, from day 1 and day 20 of diabetes confirmation. Then, rats were tested in elevated plus maze (EPM) and Morris water maze (MWM).Results:A statistically significant (p<0.05) difference was observed between the SRCT group and diabetic groups of rats. Apart from decreasing FBS, the combined therapy also proved beneficial as nootropic agent in rats with early-onset diabetes. However, significant improvement is observed only in the learning and memory among preventive group, but not in the curative group.Conclusions:SRCT, a herbal formula, when used in combination, has a more potent effect in preventing the deleterious effects of juvenile diabetes on cognitive and behavioral changes.

Clinical course of neurological disorders in experimental hemorrhagic stroke after treatment with interleukin-2 (ronkoleukinum)

Aim. To study the influence of recombinant interleukin-2 (Ronkoleukinum) on indicators of oxidative protein modification and severity of neurologic signs in rats with experimental hemorrhagic stroke. Methods. Oxidative protein modification (by aldehyde and carboxyl products), the survival rate, neurological deficit by McGrow Stroke-index and animal psychophysiological status were studied on the model of intracerebral hemorrhage in rats after treatment with 0.01 mg/kg of interleukin-2 (Ronkoleukinum). Results. The progression of experimental hemorrhagic stroke in rats was accompanied with typical pathophysiological signs - oxidative protein modification with following neurological and cognitive disorders, followed by death of experimental animals. Administration of interleukin-2 (Ronkoleukinum) 0.01 mg/kg hampered the processes of free radical proteins damage, therefore decreasing the mortality rate in animals with intracerebral hemorrhage. Animals that were administered interleukin-2 (Ronkoleukinum) died only during the first 24 hours after the stroke, with mortality rate significantly lower compared to controls starting form the 4th day of the experiment (р 0.05). The use of interleukin-2 (Ronkoleukinum) also statistically significantly decreased the severity of post-ischemic behavioral, neurological and cognitive disorders, improving the movement activity, psychoneurological status assessed by McGrow scale, stabilizing the memory and passive avoidance reflex recovery. Conclusion: interleukin-2 (Ronkoleukinum) can effectively prevent the formation of post-stroke neuronal disorders, so its use as a nosotropic nootropic agent seems to have a good perspective.