Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00141.X
A. Hainsworth, A. Stefani, P. Calabresi, T. W. Smith, M. Leach
Sipatrigine is a substituted pyrimidine derived from lamotrigine. It attenuates glutamate release in vitro and in vivo, probably as a result of sodium and calcium channel inhibition. It consistently reduces cortical infarct volume in rodent models of global, permanent focal, and transient focal ischemia (typically 50–60% reduction with maximum effective doses >20 mg/kg). Striatal protection was found in some studies but not others. The drug was effective also in a rat optic nerve model of white matter ischemia, providing complete neuroprotection at the highest concentration (100 μM) used. In monkeys, CNS penetration by sipatrigine was rapid and the steady state brain/plasma ratio was >40. In humans, low doses (< 2 mg/kg, then 1 mg/kg/8 h) were well tolerated. At higher doses a significant incidence of hallucinations and vomiting was observed. These adverse effects were speculated to be due to interactions with muscarinic receptors and 5-HT3 (or sigma) receptors, respectively. Cardiovascular side effects appeared not to be a major concern. In electrophysiological studies, sipatrigine inhibited native neuronal sodium and calcium channels (including L, N, and P/Q type) and recombinant type IIA sodium and N and T type calcium channels, all with similar potency (IC50 in the range 5–16 μM). Inhibitory potency was increased by high action potential firing frequencies and a depolarized resting voltage. These properties may account for its actions in vitro and in animal models but do not exclude possible additional actions in later stages of ischemic damage.
{"title":"Sipatrigine (BW 619C89) is a Neuroprotective Agent and a Sodium Channel and Calcium Channel Inhibitor","authors":"A. Hainsworth, A. Stefani, P. Calabresi, T. W. Smith, M. Leach","doi":"10.1111/J.1527-3458.2000.TB00141.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00141.X","url":null,"abstract":"Sipatrigine is a substituted pyrimidine derived from lamotrigine. It attenuates glutamate release in vitro and in vivo, probably as a result of sodium and calcium channel inhibition. It consistently reduces cortical infarct volume in rodent models of global, permanent focal, and transient focal ischemia (typically 50–60% reduction with maximum effective doses >20 mg/kg). Striatal protection was found in some studies but not others. The drug was effective also in a rat optic nerve model of white matter ischemia, providing complete neuroprotection at the highest concentration (100 μM) used. In monkeys, CNS penetration by sipatrigine was rapid and the steady state brain/plasma ratio was >40. In humans, low doses (< 2 mg/kg, then 1 mg/kg/8 h) were well tolerated. At higher doses a significant incidence of hallucinations and vomiting was observed. These adverse effects were speculated to be due to interactions with muscarinic receptors and 5-HT3 (or sigma) receptors, respectively. Cardiovascular side effects appeared not to be a major concern. In electrophysiological studies, sipatrigine inhibited native neuronal sodium and calcium channels (including L, N, and P/Q type) and recombinant type IIA sodium and N and T type calcium channels, all with similar potency (IC50 in the range 5–16 μM). Inhibitory potency was increased by high action potential firing frequencies and a depolarized resting voltage. These properties may account for its actions in vitro and in animal models but do not exclude possible additional actions in later stages of ischemic damage.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"13 1","pages":"111-134"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89058088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00165.X
L. Schechter
{"title":"Potential Utility of 5-HT1A Receptor Antagonists in the Treatment of Cognitive Loss Associated with Alzheimer's Disease","authors":"L. Schechter","doi":"10.1111/J.1527-3458.2000.TB00165.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00165.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"58 1","pages":"13-14"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84832797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00149.X
C. Zubaran
Ibogaine is one of the psychoactive alkaloids found in the West African shrub Tabernanthe iboga. Since the 1980s, a series of US patents have claimed efficacy for ibogaine in the treatment of drug addiction. Since then, more than 60 scientific publications on ibogaine and drug addiction have been published. Ibogaine has an acute and a prolonged effect on neurochemistry and behavior. Its metabolite, noribogaine (12-hydroxyibogamine), is produced through metabolic demethylation soon after oral ibogaine administration. Although, they share similar chemical structures, ibogaine and noribogaine display different binding profiles. In rodents both, ibogaine and noribogaine, decreased morphine and cocaine intake and modulated dopaminergic transmission. In rats trained to discriminate ibogaine from saline, complete generalization to noribogaine was obtained. Attempts to correlate brain levels of both, the parent compound and the metabolite indicate that noribogaine is primarily responsible for ibogaine discriminative stimulus. Ibogaine-induced neurotoxicity tends to occur at doses much higher than the proposed dose for humans, but caution is important when extrapolating data from ibogaine's effects observed in rodents. Although a definitive clinical validation of purported ibogaine effects is still unavailable, ibogaine has opened new perspectives in the investigation of pharmacotherapies for drug addiction.
{"title":"Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite","authors":"C. Zubaran","doi":"10.1111/J.1527-3458.2000.TB00149.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00149.X","url":null,"abstract":"Ibogaine is one of the psychoactive alkaloids found in the West African shrub Tabernanthe iboga. Since the 1980s, a series of US patents have claimed efficacy for ibogaine in the treatment of drug addiction. Since then, more than 60 scientific publications on ibogaine and drug addiction have been published. Ibogaine has an acute and a prolonged effect on neurochemistry and behavior. Its metabolite, noribogaine (12-hydroxyibogamine), is produced through metabolic demethylation soon after oral ibogaine administration. Although, they share similar chemical structures, ibogaine and noribogaine display different binding profiles. In rodents both, ibogaine and noribogaine, decreased morphine and cocaine intake and modulated dopaminergic transmission. In rats trained to discriminate ibogaine from saline, complete generalization to noribogaine was obtained. Attempts to correlate brain levels of both, the parent compound and the metabolite indicate that noribogaine is primarily responsible for ibogaine discriminative stimulus. Ibogaine-induced neurotoxicity tends to occur at doses much higher than the proposed dose for humans, but caution is important when extrapolating data from ibogaine's effects observed in rodents. Although a definitive clinical validation of purported ibogaine effects is still unavailable, ibogaine has opened new perspectives in the investigation of pharmacotherapies for drug addiction.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"27 1","pages":"219-240"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74894294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00138.X
C. Ghelardini, N. Galeotti, M. Romanelli, F. Gualtieri, A. Bartolini
Ghelardini et al. (27) reported that atropine at very low doses induces central antinociception in rodents through an enhancement of cholinergic transmission. Soon after, it was discovered that the R-(+)-enantiomer of atropine, R-(+)-hyoscyamine, was responsible for the antinociceptive activity of the racemate, while the S-(–)-enantiomer, S-(–)-hyoscyamine, was devoid of any antinociceptive action (29). R-(+)-hyoscyamine, in the same range of analgesic doses, was also able to prevent amnesia induced by antimuscarinic drugs (35). It is interesting to note that this antinociceptive activity, different from that produced by direct muscarinic agonists and cholinesterase inhibitors, was not accompanied by typical cholinergic symptoms (e.g., tremors, sialorrhea, diarrhea, rhinorrhea, lacrimation). An investigation of the antinociceptive and antiamnesic effect of atropine has demonstrated, using microdialysis techniques, that R-(+)-hyoscyamine, at cholinomimetic doses, produced an increase in acetylcholine (ACh) release from the rat cerebral cortex in vivo, indicating that it acts via a presynaptic mechanism (35). On this basis, a synthetic program to modify the chemical structure of atropine was started, which aimed to develop cholinergic amplifiers endowed with more intensive antinociceptive and antiamnesic activities than atropine but, like atropine, lacking cholinergic side effects. These compounds would, therefore, be potentially useful as analgesics and or in pathological conditions characterized by cholinergic deficits (e.g., Alzheimer’s
{"title":"Pharmacological Characterization of the Novel ACh Releaser α‐tropanyl 2‐(4‐bromophenyl)propionate (PG‐9)","authors":"C. Ghelardini, N. Galeotti, M. Romanelli, F. Gualtieri, A. Bartolini","doi":"10.1111/J.1527-3458.2000.TB00138.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00138.X","url":null,"abstract":"Ghelardini et al. (27) reported that atropine at very low doses induces central antinociception in rodents through an enhancement of cholinergic transmission. Soon after, it was discovered that the R-(+)-enantiomer of atropine, R-(+)-hyoscyamine, was responsible for the antinociceptive activity of the racemate, while the S-(–)-enantiomer, S-(–)-hyoscyamine, was devoid of any antinociceptive action (29). R-(+)-hyoscyamine, in the same range of analgesic doses, was also able to prevent amnesia induced by antimuscarinic drugs (35). It is interesting to note that this antinociceptive activity, different from that produced by direct muscarinic agonists and cholinesterase inhibitors, was not accompanied by typical cholinergic symptoms (e.g., tremors, sialorrhea, diarrhea, rhinorrhea, lacrimation). An investigation of the antinociceptive and antiamnesic effect of atropine has demonstrated, using microdialysis techniques, that R-(+)-hyoscyamine, at cholinomimetic doses, produced an increase in acetylcholine (ACh) release from the rat cerebral cortex in vivo, indicating that it acts via a presynaptic mechanism (35). On this basis, a synthetic program to modify the chemical structure of atropine was started, which aimed to develop cholinergic amplifiers endowed with more intensive antinociceptive and antiamnesic activities than atropine but, like atropine, lacking cholinergic side effects. These compounds would, therefore, be potentially useful as analgesics and or in pathological conditions characterized by cholinergic deficits (e.g., Alzheimer’s","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"24 1","pages":"63-78"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75102940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00186.X
J. Araujo, A. Chan, N. Milgram
{"title":"A Scopolamine-Induced Model of Cognitive Dysfunction in Canines","authors":"J. Araujo, A. Chan, N. Milgram","doi":"10.1111/J.1527-3458.2000.TB00186.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00186.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"29 1","pages":"43-43"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74972177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00160.X
J. Disterhoft
{"title":"Drugs that Enhance Learning in Aging Brain","authors":"J. Disterhoft","doi":"10.1111/J.1527-3458.2000.TB00160.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00160.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"12 1","pages":"4-4"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77745446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00135.X
N. Katsube, R. Ishitani
{"title":"A Review of the Neurotrophic and Neuroprotective Properties of ONO-1603: Comparison with Those of Tetrahydroaminoacridine, an Antidementia Drug","authors":"N. Katsube, R. Ishitani","doi":"10.1111/J.1527-3458.2000.TB00135.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00135.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"36 1","pages":"21-34"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72804044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00148.X
G. Marek
Activation of neocortical 5-hydroxytryptamine2A (5-HT2A) receptors is thought to mediate the profound psychomimetic effects of hallucinogenic drugs such as LSD and mescaline. These effects include alteration in mood, perception, and cognition. Conversely, blockade of neocortical 5-HT2 receptor may be related to the thymoleptic effects of newly released antidepressant (e.g., mirtazepine, nefazodone) and atypical antipsychotic drugs (e.g., risperidone, olanzapine). Therefore, one strategy to develop novel antidepressant drugs might be to identify drugs which suppress the effects of 5-HT2A receptor activation in key neurocircuits. Electrophysiological experiments using in vitro rat slices of the medial prefrontal cortex have found that activation of 5-HT2A receptors results in glutamate release from thalamocortical terminals by a novel focal effect. A number of monoamine (5-HT1/7, β2), metabotropic glutamate (mGlu2), and neuropeptide (μ-opioid) receptors suppress the glutamate release induced by 5-HT2A receptor activation. Clinical studies examining the effects of serotonin or catecholamine depletion suggest the activation of 5-HT or catecholamine receptors mediate the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), respectively. In addition, opiate agonists may have antidepressant properties. Therefore, it is suggested that elucidation of the specific receptors that suppress glutamate release induced by 5-HT2A receptor activation in the medial prefrontal cortex may have several effects. First, this might lead to a more complete understanding of the 5-HT receptor(s) that mediate the therapeutic effects of presently used drugs such as SSRIs. This site might be a therapeutic target free of side effects such as sexual dysfunction. Second, this strategy might lead to novel therapeutic targets for depression, such as metabotropic glutamate agonists which may not be efficacious in screening strategies primarily dependent on synaptic availability of monoaminergic neurotransmitters.
{"title":"A Novel Approach to the Identification of Psychiatric Drugs: Serotonin-Glutamate Interactions in the Prefrontal Cortex","authors":"G. Marek","doi":"10.1111/J.1527-3458.2000.TB00148.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00148.X","url":null,"abstract":"Activation of neocortical 5-hydroxytryptamine2A (5-HT2A) receptors is thought to mediate the profound psychomimetic effects of hallucinogenic drugs such as LSD and mescaline. These effects include alteration in mood, perception, and cognition. Conversely, blockade of neocortical 5-HT2 receptor may be related to the thymoleptic effects of newly released antidepressant (e.g., mirtazepine, nefazodone) and atypical antipsychotic drugs (e.g., risperidone, olanzapine). Therefore, one strategy to develop novel antidepressant drugs might be to identify drugs which suppress the effects of 5-HT2A receptor activation in key neurocircuits. Electrophysiological experiments using in vitro rat slices of the medial prefrontal cortex have found that activation of 5-HT2A receptors results in glutamate release from thalamocortical terminals by a novel focal effect. A number of monoamine (5-HT1/7, β2), metabotropic glutamate (mGlu2), and neuropeptide (μ-opioid) receptors suppress the glutamate release induced by 5-HT2A receptor activation. Clinical studies examining the effects of serotonin or catecholamine depletion suggest the activation of 5-HT or catecholamine receptors mediate the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), respectively. In addition, opiate agonists may have antidepressant properties. Therefore, it is suggested that elucidation of the specific receptors that suppress glutamate release induced by 5-HT2A receptor activation in the medial prefrontal cortex may have several effects. First, this might lead to a more complete understanding of the 5-HT receptor(s) that mediate the therapeutic effects of presently used drugs such as SSRIs. This site might be a therapeutic target free of side effects such as sexual dysfunction. Second, this strategy might lead to novel therapeutic targets for depression, such as metabotropic glutamate agonists which may not be efficacious in screening strategies primarily dependent on synaptic availability of monoaminergic neurotransmitters.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"337 1","pages":"206-218"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75477972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2001.TB00199.X
R. Nadal
Remoxipride is a substituted benzamide that acts as a weak but very selective antagonist of dopamine D2 receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. This article reviews its putative selective effects on mesolimbic versus nigrostriatal dopaminergic systems. In animals, remoxipride has minimal cataleptic effects at doses that block dopamine agonist-induced hyperactivity. These findings are predictive of antipsychotic activity with a low likelihood of extrapyramidal symptoms. Remoxipride also appears to be effective in more recent animal models of schizophrenia, such as latent inhibition or prepulse inhibition. In clinical studies, remoxipride shows a relatively low incidence of extrapyramidal side effects and its effects on prolactin release are short-lasting and generally mild. The clinical efficacy of remoxipride is similar to that of haloperidol or chlorpromazine. Although its clinical use was severely restricted in 1993, due to reports of aplastic anemia in some patients receiving remoxipride, this drug has been found to exhibit relatively high selectivity for dopamine D2 receptors making remoxipride an interesting tool for neurochemical and behavioral studies.
{"title":"Pharmacology of the atypical antipsychotic remoxipride, a dopamine D2 receptor antagonist.","authors":"R. Nadal","doi":"10.1111/J.1527-3458.2001.TB00199.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00199.X","url":null,"abstract":"Remoxipride is a substituted benzamide that acts as a weak but very selective antagonist of dopamine D2 receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. This article reviews its putative selective effects on mesolimbic versus nigrostriatal dopaminergic systems. In animals, remoxipride has minimal cataleptic effects at doses that block dopamine agonist-induced hyperactivity. These findings are predictive of antipsychotic activity with a low likelihood of extrapyramidal symptoms. Remoxipride also appears to be effective in more recent animal models of schizophrenia, such as latent inhibition or prepulse inhibition. In clinical studies, remoxipride shows a relatively low incidence of extrapyramidal side effects and its effects on prolactin release are short-lasting and generally mild. The clinical efficacy of remoxipride is similar to that of haloperidol or chlorpromazine. Although its clinical use was severely restricted in 1993, due to reports of aplastic anemia in some patients receiving remoxipride, this drug has been found to exhibit relatively high selectivity for dopamine D2 receptors making remoxipride an interesting tool for neurochemical and behavioral studies.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"16 1","pages":"265-82"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85472336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2006-06-07DOI: 10.1111/j.1527-3458.2004.tb00014.x
X. Jiang-ping, Wu Hang-yu, Li Lin, S. Sha
Objective: To investigate the effects of Capsule Yi-Zhi (CYZ is extracted and purified by our department mainly from Polygonum Multiflorum, Ginseng and Korean Epimedium herb, among which quantitatively effective ingredients are more than 50%.) on learning and memory disorder and â-amyloid protein induced neurotoxicity in rats. Methods: Various doses of CYZ were administered to Sprague-Dawley (SD) rats for 8 days, twice a day. Then scopolamine hydrobromide (Sco) intraperitoneal injection was performed on each rat and the Morris water maze test and step-though test were carried out respectively to explore the changes of the rats’ learning and memory capacities. Primary rat cortex neurons were cultured in vitro for 7 days and then, serum containing CYZ was added to neurons before or after the addition of â Amyloid peptide25–35 (Aâ25–35) to see the extent of CYZ’s protectiveness on neurotoxicity. MTT assay and test of level of LDH in the culture media were performed to achieve this aim. Results Compared with control group, rats in Morris water maze test required significantly decreased time in finding the platform under the water surface from 19.5 ± 11.40 to 8.5 ± 2.39, 8.8 ± 3.07, and 7.4 ± 3.87 sec, respectively, and in step-though test, the latent period rose from 22.70 ± 23.07 to 148.50 ± 124.02, 176.50 ± 143.36, and 196.60 ± 128.00 sec and the error number decreased from 14.20 ± 7.74 to 7.50 ± 8.02, 3.40 ± 4.43 and 2.50 ± 3.10 respectively, all with statistical significance. Moreover, in cultured primary neurons, the dramatic drop of LDH level in culture media from 3670.2 ± 437.65 to 864.5 ± 371.69 and 1444 ± 635.18 U L and the high A scores rising from 0.68 ± 0.193 to 0.93 ± 0.009 and 0.96 ± 0.239 in MTT test indicated that CYZ could effectively resist the neurotoxicity induced by Aâ25–35. Conclusions: CYZ presented promising effects on learning and memory dysfunction and Aâ induced neurotoxicity in vitro.
{"title":"Effects of Capsule Yi‐Zhi on Learning and Memory Disorder and β‐Amyloid Peptide Induced Neurotoxicity in Rats","authors":"X. Jiang-ping, Wu Hang-yu, Li Lin, S. Sha","doi":"10.1111/j.1527-3458.2004.tb00014.x","DOIUrl":"https://doi.org/10.1111/j.1527-3458.2004.tb00014.x","url":null,"abstract":"Objective: To investigate the effects of Capsule Yi-Zhi (CYZ is extracted and purified by our department mainly from Polygonum Multiflorum, Ginseng and Korean Epimedium herb, among which quantitatively effective ingredients are more than 50%.) on learning and memory disorder and â-amyloid protein induced neurotoxicity in rats. Methods: Various doses of CYZ were administered to Sprague-Dawley (SD) rats for 8 days, twice a day. Then scopolamine hydrobromide (Sco) intraperitoneal injection was performed on each rat and the Morris water maze test and step-though test were carried out respectively to explore the changes of the rats’ learning and memory capacities. Primary rat cortex neurons were cultured in vitro for 7 days and then, serum containing CYZ was added to neurons before or after the addition of â Amyloid peptide25–35 (Aâ25–35) to see the extent of CYZ’s protectiveness on neurotoxicity. MTT assay and test of level of LDH in the culture media were performed to achieve this aim. Results Compared with control group, rats in Morris water maze test required significantly decreased time in finding the platform under the water surface from 19.5 ± 11.40 to 8.5 ± 2.39, 8.8 ± 3.07, and 7.4 ± 3.87 sec, respectively, and in step-though test, the latent period rose from 22.70 ± 23.07 to 148.50 ± 124.02, 176.50 ± 143.36, and 196.60 ± 128.00 sec and the error number decreased from 14.20 ± 7.74 to 7.50 ± 8.02, 3.40 ± 4.43 and 2.50 ± 3.10 respectively, all with statistical significance. Moreover, in cultured primary neurons, the dramatic drop of LDH level in culture media from 3670.2 ± 437.65 to 864.5 ± 371.69 and 1444 ± 635.18 U L and the high A scores rising from 0.68 ± 0.193 to 0.93 ± 0.009 and 0.96 ± 0.239 in MTT test indicated that CYZ could effectively resist the neurotoxicity induced by Aâ25–35. Conclusions: CYZ presented promising effects on learning and memory dysfunction and Aâ induced neurotoxicity in vitro.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"66 1","pages":"192-192"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85795414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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