The Experts below are selected from a list of 966 Experts worldwide ranked by ideXlab platform
Mitsunobu Yoshii - One of the best experts on this subject based on the ideXlab platform.
-
Neuronal Ca2+ Channels and Nicotinic ACh Receptors as Functional Targets of the Nootropic Nefiracetam
Psychogeriatrics, 2001Co-Authors: Mitsunobu Yoshii, Shigeo Watabe, Tomoyuki Nishizaki, Tadashi Shiotani, Yoshiya L. Murashima, Toshihide NukadaAbstract:: Piracetam-like Nootropics (or cognitive enhancers) have been used for the treatment of various forms of dementia, including Alzheimer's disease. The underlying mechanisms of their actions, however, are largely unknown. Our recent studies have demonstrated that nefiracetam, a Nootropic Agent, can markedly enhance activities of neuronal L-and N-type (α1B) Ca2+ channels as well as those of presynaptic nicotinic acetylcholine (ACh) receptors, thereby increasing neurotransmitter release. Aniracetam exerted a slight facilitatory effect on Ca2+ channels, but no effect on nicotinic ACh receptors. Piracetam and oxiracetam have no such actions on Ca2+ channels and nicotinic ACh receptors. It is suggested that inhibitory G-proteins (Go/Gi) and protein kinase A (PKA) mediate the nefiracetam action on Ca2+ channels, whereas protein kinase C (PKC) mediates the drug action on nicotinic ACh receptors. In the hippocampus of the rodent, nefiracetam induces a long-lasting (>4 h) facilitation of synaptic transmission. The ‘LTP-like’ facilitation appears to result from activation of presynaptic nicotinic ACh receptors (and Ca2+ channels as well) by nefiracetam. In conclusion, nefiracetam is distinguished from other Nootropic Agents for its preferential actions on both presynaptic Ca2+ channels and nicotinic ACh receptors, and could therefore be of great therapeutic importance to the neurotransmission failure that contributes to the symptoms of Alzheimer's disease and associated disorders.
-
a long term potentiation like facilitation of hippocampal synaptic transmission induced by the Nootropic nefiracetam
Brain Research, 1999Co-Authors: Tomoyuki Nishizaki, Mitsunobu Yoshii, Shigeo Watabe, Toshiyuki Matsuoka, Tamotsu Nomura, Shogo Matsuyama, Tadashi ShiotaniAbstract:Nefiracetam, a Nootropic Agent, enhanced the slope of field excitatory postsynaptic potentials in the CA1 region of rat hippocampal slices to about 170% of basal levels, being evident still at 4-h washing-out of the drug. A similar sustained enhancement (≥16 h after i.m. injection with nefiracetam) was observed in the population spikes recorded from the granular cell layer of the intact mouse hippocampus. Saturation of the enhancement in the synaptic strength occluded potentiation obtained with long-term potentiation (LTP) induced by high-frequency (tetanic) stimulation, and vice versa. Interestingly, the facilitatory action of nefiracetam was blocked by either the nicotinic acetylcholine (ACh) receptor antagonists, α-bungarotoxin and mecamylamine, or the selective protein kinase C (PKC) inhibitor, GF109203X, but in contrast, it was not affected by d-2-amino-5-phosphonovaleric acid (APV), a selective N-methyl-d-aspartate (NMDA) receptor antagonist. The results of the present study suggest that nefiracetam, whereas the action is independent of NMDA receptors, induces an `LTP-like' facilitation of hippocampal synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a likely mechanism underlying the cognition-enhancing actions of nefiracetam.
-
enhancement of neuronal calcium channel currents by the Nootropic Agent nefiracetam dm 9384 in ng108 15 cells
Brain Research, 1994Co-Authors: Mitsunobu Yoshii, Shigeo WatabeAbstract:Abstract Effects of Nootropic Agents on neuronal calcium channels were studied in NG108-15 cells using the whole-cell patch-clamp technique. Nefiracetam (DM-9384) at a concentration of 1 μM increased a long-lasting component of calcium channel currents two-fold without affecting a transient component. The dose-response relationship yielded a bell-shaped curve with a peak at 1 μM. Similar, but slightly less potent effects were observed by aniracetam. Dibutyryl cyclic AMP (1 mM) also enhanced the currents, which were not further increased by nefiracetam, or vice versa. The currents enhanced by nefiracetam were markedly reduced by nifedipine (10 μM), an ‘L-type’ calcium channel blocker. Cells treated with pertussis toxin (PTX; 500ng/ml, > 20h) to inactivate inhibitory G-proteins were apparently insensitive to nefiracetam. The results suggest that the Nootropic Agents may enhance the activity of neuronal L-type calcium channels under the regulation of inhibitory G-proteins and possibly, cyclic AMP-dependent processes.
Hanumanthachar Joshi - One of the best experts on this subject based on the ideXlab platform.
-
Revista Brasileira de Ciências Farmacêuticas Brazilian Journal of Pharmaceutical Sciences
2016Co-Authors: Hanumanthachar Joshi, Krupa MegeriAbstract:Clerodendron phlomidis Linn. (Verbenaceae) is known as Agnimantha in sanskrit. Bark of the plant is used in treating various nervous disorders. In the present study C. phlomidis was investigated for its potential as a Nootropic Agent in mice. The aqueous extract of the C. phlomidis (100 and 200 mg/kg, p.o.) was administered for 6 successive days to both young and aged mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate short term and long term memory respectively. Scopolamine (0.4 mg/kg, i.p.), diazepam (1 mg/kg, i.p.) were employed to induce amnesia in mice. To delineate the mechanism by which C. phlomidis exerts Nootropic action, its effect on brain acetyl cholinesterase levels were determined. Piracetam (200 mg/kg, i.p.) was used as a standard Nootropic Agent. Pretreatment with C. phlomidis (100 and 200 mg/ kg, p.o.) for 6 successive days significantly improved learning and memory in mice. It reversed the amnesia induced by scopolamine, diazepam and natural ageing. It also decreased the acetyl cholinesterase levels in the whole brain. The bark of C. phlomidis can be of enormous use in the management of treatment of cognitive disorders such as amnesia and Alzheimer’s disease
-
P03-81 - Cognition improving effects of clerodendron phlomidis linn. bark extract in mice
European Psychiatry, 2011Co-Authors: Hanumanthachar Joshi, Krupa MegeriAbstract:Normal ageing is known to deteriorate memory in human beings. Oxygen free radicals, the harmful byproducts of oxidative metabolism are known to cause organic damage to the living system, which may be responsible for the development of Alzheimer's disease in elderly. Clerodendron phlomidis Linn. (Verbenaceae) is known as Agnimantha in sanskrit. Bark of the plant is used in treating various nervous disorders. In the present study C. phlomidis was investigated for its potential as a Nootropic Agent in mice. The aqueous extract of the C. phlomidis (100 and 200 mg/kg, p.o.) was administered for 6 successive days to both young and aged mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate short term and long term memory respectively. Scopolamine, diazepam were used to induce amnesia in mice. To delineate the mechanism by which C. phlomidis exerts Nootropic action, its effect on brain acetyl cholinesterase levels were determined. Piracetam was used as a standard Nootropic Agent. Pretreatment with C. phlomidis (100 and 200 mg/kg, p.o.) for 6 successive days significantly improved learning and memory in mice. It reversed the amnesia induced by scopolamine, diazepam and natural ageing. It also decreased the acetyl cholinesterase levels in the whole brain. The bark of C. phlomidis can be useful in treatment of cognitive disorders such as amnesia and Alzheimer's disease.
-
Evaluation of Antiamnesic Potentials of Calotropis Procera in Mice
2009Co-Authors: C. C. Gavimath, Hanumanthachar Joshi, P. PattarAbstract:Alzheimer’s disease (AD) is the most common cause of a medical condition known as dementia, which effects the brain and hence memory. The National Institute of Health predicts, if the current trend continues, there will be more than 8.5 million AD patients by the year 2030 in USA alone. Although there is no cure for dementia if AD type at present alternative pharmacologic treatment modalities can reduce the symptoms of cognitive improvement and slow disease progression. Nootropic Agents like, piracetam and cholinesterase inhibitors like, Donepezil® are commonly used for improving memory, mood and behavior. However, the resulting adverse effects of these drugs have limited their use and it is worthwhile to explore the utility of traditional medicines in the treatment of various cognitive disorders. The present work was undertaken to assess the potential of latex of Calotropis procera as a Nootropic Agent in mice. Elevated plus maze was employed to assess the memory of mice. Whole brain Ache activity was also measured. Diazepam (1 mg/kg, i.p.) and Scopolamine (0.4 mg/kg,i.p.) were used to induce amnesia in mice. C. procera (100 and 200 mg/Kg, p.o.) was administered for 3 successive days to both young and old aged mice. C. procera deceased transfer latencies indicating improvement in learning and memory and it also reversed amnesia induced by Scopolamine, diazepam and natural ageing. Hence C. procera can be employed as a memory restoration Agent in patients suffering from amnesia.
-
Antiamnesic Effects of Desmodium gangeticum in Mice
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2006Co-Authors: Hanumanthachar Joshi, Milind ParleAbstract:Dementia is a mental disorder characterized by loss of intellectual ability sufficiently severe enough to interfere with one's occupational or social activities. Desmodium gangeticum commonly known as Salparni, is widely used in ayurveda for the treatment of neurological disorders. The present work was designed to assess the potential of aqueous extract of D. gangeticum (DG) as a Nootropic Agent in mice. DG (50, 100 and 200 mg/kg, p.o.) was administered for 7 successive days to both young and older mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory. Scopolamine (0.4 mg/kg, i.p.) induced amnesia and ageing induced amnesia were the interoceptive behavioral models. To delineate the mechanism by which DG exerts Nootropic activity, the effect of DG on whole brain AChE activity was also assessed. Piracetam (200 mg/kg, i.p.) was used as a standard Nootropic Agent. Pretreatment with DG (50, 100 and 200 mg/kg p.o.) for seven successive days significantly improved learning and memory in mice and reversed the amnesia induced by both, scopolamine (0.4 mg/kg, i.p.) and natural ageing. DG also decreased whole brain acetyl cholinesterase activity. Hence, D. gangeticum appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of dementia and Alzheimer disease.
-
Brahmi rasayana Improves Learning and Memory in Mice
Evidence-based complementary and alternative medicine : eCAM, 2006Co-Authors: Hanumanthachar Joshi, Milind ParleAbstract:Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic Agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil® are being used to improve memory, mood and behavior, but the resulting side effects associated with these Agents have made their use limited. The present study was undertaken to assess the potential of Brahmi rasayana (BR) as a memory enhancer. BR (100 and 200 mg kg−1 p.o.) was administered for eight successive days to both young and aged mice. Elevated plus maze and passive-avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg kg−1 i.p.) was used to induce amnesia in mice. The effect of BR on whole brain AChE activity was also assessed. Piracetam (200 mg kg−1 i.p.) was used as a standard Nootropic Agent. BR significantly improved learning and memory in young mice and reversed the amnesia induced by both scopolamine (0.4 mg kg−1 i.p.) and natural aging. BR significantly decreased whole brain acetyl cholinesterase activity. BR might prove to be a useful memory restorative Agent in the treatment of dementia seen in elderly.
Shigeo Watabe - One of the best experts on this subject based on the ideXlab platform.
-
Neuronal Ca2+ Channels and Nicotinic ACh Receptors as Functional Targets of the Nootropic Nefiracetam
Psychogeriatrics, 2001Co-Authors: Mitsunobu Yoshii, Shigeo Watabe, Tomoyuki Nishizaki, Tadashi Shiotani, Yoshiya L. Murashima, Toshihide NukadaAbstract:: Piracetam-like Nootropics (or cognitive enhancers) have been used for the treatment of various forms of dementia, including Alzheimer's disease. The underlying mechanisms of their actions, however, are largely unknown. Our recent studies have demonstrated that nefiracetam, a Nootropic Agent, can markedly enhance activities of neuronal L-and N-type (α1B) Ca2+ channels as well as those of presynaptic nicotinic acetylcholine (ACh) receptors, thereby increasing neurotransmitter release. Aniracetam exerted a slight facilitatory effect on Ca2+ channels, but no effect on nicotinic ACh receptors. Piracetam and oxiracetam have no such actions on Ca2+ channels and nicotinic ACh receptors. It is suggested that inhibitory G-proteins (Go/Gi) and protein kinase A (PKA) mediate the nefiracetam action on Ca2+ channels, whereas protein kinase C (PKC) mediates the drug action on nicotinic ACh receptors. In the hippocampus of the rodent, nefiracetam induces a long-lasting (>4 h) facilitation of synaptic transmission. The ‘LTP-like’ facilitation appears to result from activation of presynaptic nicotinic ACh receptors (and Ca2+ channels as well) by nefiracetam. In conclusion, nefiracetam is distinguished from other Nootropic Agents for its preferential actions on both presynaptic Ca2+ channels and nicotinic ACh receptors, and could therefore be of great therapeutic importance to the neurotransmission failure that contributes to the symptoms of Alzheimer's disease and associated disorders.
-
a long term potentiation like facilitation of hippocampal synaptic transmission induced by the Nootropic nefiracetam
Brain Research, 1999Co-Authors: Tomoyuki Nishizaki, Mitsunobu Yoshii, Shigeo Watabe, Toshiyuki Matsuoka, Tamotsu Nomura, Shogo Matsuyama, Tadashi ShiotaniAbstract:Nefiracetam, a Nootropic Agent, enhanced the slope of field excitatory postsynaptic potentials in the CA1 region of rat hippocampal slices to about 170% of basal levels, being evident still at 4-h washing-out of the drug. A similar sustained enhancement (≥16 h after i.m. injection with nefiracetam) was observed in the population spikes recorded from the granular cell layer of the intact mouse hippocampus. Saturation of the enhancement in the synaptic strength occluded potentiation obtained with long-term potentiation (LTP) induced by high-frequency (tetanic) stimulation, and vice versa. Interestingly, the facilitatory action of nefiracetam was blocked by either the nicotinic acetylcholine (ACh) receptor antagonists, α-bungarotoxin and mecamylamine, or the selective protein kinase C (PKC) inhibitor, GF109203X, but in contrast, it was not affected by d-2-amino-5-phosphonovaleric acid (APV), a selective N-methyl-d-aspartate (NMDA) receptor antagonist. The results of the present study suggest that nefiracetam, whereas the action is independent of NMDA receptors, induces an `LTP-like' facilitation of hippocampal synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a likely mechanism underlying the cognition-enhancing actions of nefiracetam.
-
enhancement of neuronal calcium channel currents by the Nootropic Agent nefiracetam dm 9384 in ng108 15 cells
Brain Research, 1994Co-Authors: Mitsunobu Yoshii, Shigeo WatabeAbstract:Abstract Effects of Nootropic Agents on neuronal calcium channels were studied in NG108-15 cells using the whole-cell patch-clamp technique. Nefiracetam (DM-9384) at a concentration of 1 μM increased a long-lasting component of calcium channel currents two-fold without affecting a transient component. The dose-response relationship yielded a bell-shaped curve with a peak at 1 μM. Similar, but slightly less potent effects were observed by aniracetam. Dibutyryl cyclic AMP (1 mM) also enhanced the currents, which were not further increased by nefiracetam, or vice versa. The currents enhanced by nefiracetam were markedly reduced by nifedipine (10 μM), an ‘L-type’ calcium channel blocker. Cells treated with pertussis toxin (PTX; 500ng/ml, > 20h) to inactivate inhibitory G-proteins were apparently insensitive to nefiracetam. The results suggest that the Nootropic Agents may enhance the activity of neuronal L-type calcium channels under the regulation of inhibitory G-proteins and possibly, cyclic AMP-dependent processes.
Tatiana A Gudasheva - One of the best experts on this subject based on the ideXlab platform.
-
Cyclopropyl glycine and proline-containing preparation noopept evoke two types of membrane potential responses in synaptoneurosomes.
Bulletin of experimental biology and medicine, 2003Co-Authors: V. K. Lutsenko, Tatiana A Gudasheva, M. N. VukolovaAbstract:Proline, cyclo(Pro-Gly), and acyl-prolyl-containing dipeptide GVS-111 decreased synaptoneurosome membrane potential in a Ca2+-free medium. The efficiency of these preparations decreased in the following order: GVS>cyclo(Pro-Gly)>proline. Depolarization responses induced by endogenous Nootropic Agent cyclo(Pro-Gly) was dose-dependent and saturable; the threshold concentration of cyclo(Pro-Gly) was 10-9 M. In a Ca2+-containing medium GVS and cyclo(Pro-Gly) induced both hyperpolarizing and depolarizing membrane responses of synaptoneurosomes. Possible mechanisms underlying changes in the membrane potential of synaptoneurosomes induced by Nootropic Agents are discussed. It was interesting whether modulation of electrogenesis can improve memory and potentiate the neuroprotective effect of the test Nootropic Agents.
-
effect of the novel dipeptide Nootropic Agent noopept and its metabolite cyclo l prolylglycine on the transcallosal evoked potential in the rat brain
Eksperimental'naia i klinicheskaia farmakologiia, 2002Co-Authors: G M Molodavkin, Tatiana A Gudasheva, T. A. Voronina, Sergey B. Seredenin, Gilyana Borlikova, R U Ostrovskaia, N A TushmalovaAbstract:The effect of new Nootropic dipeptides--noopept (N-phenylacetyl-L-prolylglycine, GVS-111) and its metabolite (cyclo-L-prolylglycine)--and a standard nootrope piracetam on the transcallosal evoked potential (TEP) in rat brain was studied. In the dose range from 150 to 300 mg/kg, piracetam increased the TEP amplitude, which exhibited a maximum after 1.5-2 h and then gradually decreased. Both noopept and cyclo-L-prolylglycine also increased the TEP amplitude, which attained a plateau and retained this level over the entire observation time (above 3.5 h). All the nootropes studied increased both components of the evoked potential. Piracetam and cyclo-L-prolylglycine led to an approximately equal increase in both waves, while noopept induced a somewhat greater increase in the negative TEP wave amplitude. It is suggested that the positive effect of noopept and cyclo-L-prolylglycine upon the interhemispheric signal transfer (indicated by the improved transcallosal response) can be considered as a potential neurophysiological basis for a positive drug influence on the behavioral level.
-
Anti-inflammatory properties of noopept (dipeptide Nootropic Agent GVS-111)
Eksperimental'naia i klinicheskaia farmakologiia, 2002Co-Authors: L. P. Kovalenko, Tatiana A Gudasheva, M G Miramedova, S V Alekseeva, Sergey B. SeredeninAbstract:It is established that single intravenous (0.5 and 5 mg/kg, p.o.) or single peroral (10, 50, 100 mg/kg) and prolonged peroral (5 mg/kg, over 10 days) administration of noopept produces a dose-dependent inhibition of the model inflammatory response to concanavaline A in CBA mice. Intravenously injected (5 mg/kg) noopept suppressed the acute nonimmune carrageenan-induced foot inflammation in rats by 62.2% within 3 h. The most pronounced antiinflammatory effect of dipeptide was observed on the model of adjuvant arthritis in rats, where the drug administered over 25 days in a daily dose of 0.5 mg/kg (i.m.) or 5 mg/kg (p.o.) significantly reduced the chronic immune inflammation (on the 12th day, by 94.0 and 74.1%, respectively). The in vitro experiments with neutrophilic leukocytes of F1(CBA.C57BL/6) mice treated with noopept in a single dose of 5 mg/kg (i.v.) showed a 5- to 6-fold suppression of the hemiluminescence stimulated by opsoinized zymosan or phorbolmyristate acetate. It is suggested that the antiinflammatory activity of noopept is probably related to its antioxidant properties.
-
Modulation of long-term memory by delayed administration of the amide of L-pyroglutamyl-D-alanine, a Nootropic Agent, in spaced and massed training in rats
Neuroscience and Behavioral Physiology, 1999Co-Authors: A. L. Vysotskii, Tatiana A Gudasheva, D. L. Vysotskii, R. U. Ostrovskaya, K. V. AnokhinAbstract:The effects of the Nootropic Agent L-pyroglutamyl-D-alanine amide (given at a dose of 0.5 mg/kg i.p., 24 h after training) on long-term memory were studied in rats with contextual and conditioned reflex freezing. Spaced and massed training protocols were used; habit formation was tested 72 h after training. In massed training, which led to lower levels of learning as compared with spaced training, the dipeptide improved contextual memory, while in spaced training, which led to higher initial learning levels, dosage with dipeptide improved reproduction of the habit. Testing of responses to the conditioned signal (a sound) 96 h after training, revealed no significant differences between groups. This is evidence for the selectivity of the effect of L-pyroglutamyl-D-alanine amide for contextual memory.
-
modulation of the long term memory by delayed administration of the Nootropic Agent l pyroglutamyl d alaninamide during spaced and massed training of rats
Fiziologicheskiĭ zhurnal, 1998Co-Authors: A L Vysotskiĭ, Tatiana A Gudasheva, K. V. Anokhin, R U Ostrovskaia, D L VysotskiĭAbstract:L-pyroglutamyl-D-alanine amide significantly enhanced freezing response in the group of rats with massed training and reduced it in the group with spaced training. The control animals revealed a higher freezing response with the spaced training. No differences occurred between the groups in a cue test.
E. I. Solntseva - One of the best experts on this subject based on the ideXlab platform.
-
cyclic gmp mimicks potentiation effect of the Nootropic Agent vinpocetine on the high threshold a current in the mollusk neurons
Fiziologicheskiĭ zhurnal, 1998Co-Authors: E. I. Solntseva, Iu V BukanovaAbstract:High-threshold transient K+ current (IAht) was recorded using a two-microelectrode voltage clamp technique in isolated neurons of the land snail. Effect of the Nootropic drug vinpocetine on this current was studied and compared with cyclic nucleotides. The drug either enhanced or left unaltered the IAht, and dibutyryl cyclic GMP (dcGMP) imitated the effect. These two effects were not additive. Dibutyryl cyclic AMP did not imitate, the vinpocetine effect and decreased the amplitude of the IAht. The findings suggest that the cGMP mediated the vinpocetine effect on the Iaht.
-
Nootropic Agent vinpocetine blocks delayed rectified potassium currents more strongly than high-threshold calcium currents
Neuroscience and Behavioral Physiology, 1998Co-Authors: Yu. V. Bukanova, E. I. SolntsevaAbstract:A two-microelectrode potential clamping method was used on isolated common snail neurons to measure high-threshold Ca^2+ and delayed rectified K^+ currents. Addition of the Nootropic Agent vinpocetine (VPC) to the bathing solution rapidly and reversibly inhibited both types of current. The effects of VPC were dosedependent and were independent of the test stimulus voltage. Maximum blockade of the Ca^2+ current averaged 27% at a VPC concentration of 600 μM. Maximum blockade of the K^+ current averaged 76% at a VPC concentration of 30 μM. It is concluded that K^+ channels are more likely targets of VPC than Ca^2+ channels.
-
the Nootropic Agent vinpocetine blocks the delayed rectifier potassium channel more strongly than the high conductance calcium channel
Zhurnal vyssheĭ nervnoĭ deiatelnosti imeni I P Pavlova, 1996Co-Authors: Iu V Bukanova, E. I. SolntsevaAbstract:In isolated neurons of Helix snail high-threshold Ca(2+)- and K(+)-currents were recorded using two-microelectrode voltage clamp technique. Extracellular application of Nootropic drug vinpocetine rapidly and reversibly blocked both types of current. Vinpocetine effects were dose-dependent and voltage-independent. The maximal effect of Ca(2+)-current blockade was 27% during application of vinpocetine in the concentration of 600 mcM. The maximal blockade of K(+)-current was 75% when the drug was applied in the concentration of 30 mcM. Results suggest that K(+)-channels are more probable targets for vinpocetine than Ca(2+)-channels.
