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.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.TB00143.X
R. Newcomb, Xiao-hua Chen, Robin Dean, G. Dayanithi, Cong Ruth, B. Szoke, J. Lemos, S. Bowersox, G. Miljanich
Calcium channels are represented by at least 9 distinct genes (calcium channel classes A-I), corresponding to at least 5 functional and pharmacological “types” (L, N, P/Q, R and T). Selective L-, N-, and T-type channel antagonists are either in clinical use or in late stage clinical trials, while antagonists of P/Q channels are known to be toxic. No selective ligand has been identified for the R-type (class E), and its function and pharmacology are consequently, poorly understood. We review recent work on the discovery and initial characterization of SNX-482, the first known selective antagonist of R-type calcium channels. SNX-482 is a 41 residue acidic peptide with three disulfide bonds that has been isolated from the venom of the African tarantula, Hysterocrates gigas. In cell-based assays, it is a potent and selective inhibitor of the class E or R-type calcium channel. SNX-482 blocks some but not all native R-type currents: it blocks an R-type current in vertebrate neurohypophysis, but it does not block an R-type current in cerebellar granule cells. The peptide blocks oxytocin but not vasopressin release, suggesting a possible utility for SNX-482 as a neuroendocrine modulator. The peptide possesses antiseizure activity in several animal models of epilepsy, suggesting that class E antagonists may have pharmacological use in seizure disorders.
{"title":"SNX‐482: A Novel Class E Calcium Channel Antagonist from Tarantula Venom","authors":"R. Newcomb, Xiao-hua Chen, Robin Dean, G. Dayanithi, Cong Ruth, B. Szoke, J. Lemos, S. Bowersox, G. Miljanich","doi":"10.1111/J.1527-3458.2000.TB00143.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00143.X","url":null,"abstract":"Calcium channels are represented by at least 9 distinct genes (calcium channel classes A-I), corresponding to at least 5 functional and pharmacological “types” (L, N, P/Q, R and T). Selective L-, N-, and T-type channel antagonists are either in clinical use or in late stage clinical trials, while antagonists of P/Q channels are known to be toxic. No selective ligand has been identified for the R-type (class E), and its function and pharmacology are consequently, poorly understood. We review recent work on the discovery and initial characterization of SNX-482, the first known selective antagonist of R-type calcium channels. SNX-482 is a 41 residue acidic peptide with three disulfide bonds that has been isolated from the venom of the African tarantula, Hysterocrates gigas. In cell-based assays, it is a potent and selective inhibitor of the class E or R-type calcium channel. SNX-482 blocks some but not all native R-type currents: it blocks an R-type current in vertebrate neurohypophysis, but it does not block an R-type current in cerebellar granule cells. The peptide blocks oxytocin but not vasopressin release, suggesting a possible utility for SNX-482 as a neuroendocrine modulator. The peptide possesses antiseizure activity in several animal models of epilepsy, suggesting that class E antagonists may have pharmacological use in seizure disorders.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"386 1","pages":"153-173"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77684760","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.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.TB00136.X
Y. Maruyama, H. Kuribara
This paper provides an overview of the pharmacological features of honokiol (3′,5-di-2-propenyl-1,1′-biphenyl-2,4′-diol), an isomer of neolignans isolated and identified from the stem bark of Magnoliaceous plants (Magnolia obovata Thunb, Wa-Koboku in Japanese). The magnolia bark has been utilized as a herbal remedy for the treatment of a wide variety of clinical disorders. Honokiol and magnolol (an isomer of honokiol) were recently identified as anxiolytic agents in the extracts of Saiboku-to, an oriental herbal medicine (Kampo). Behavioral evaluation through an elevated plus-maze test demonstrated that honokiol, 0.2–2 mg/kg, p.o., for 7 days, was at least 5000 times more potent than Saiboku-to. Honokiol has a comparatively lower risk of causing benzodiazepine-like side effects, such as central depression, muscle relaxation, amnesia, or physical dependence. In addition to these central actions, a wide variety of pharmacological effects and biochemical activities of honokiol have been reported during the past 10 years. The main effects, including the limited information regarding the metabolism and kinetics of the compound, are briefly introduced in this text. Information available on honokiol, including its specific and simple chemical structure, suggests the possibility of deriving more potent compounds in the drug design process.
{"title":"Overview of the Pharmacological Features of Honokiol","authors":"Y. Maruyama, H. Kuribara","doi":"10.1111/J.1527-3458.2000.TB00136.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00136.X","url":null,"abstract":"This paper provides an overview of the pharmacological features of honokiol (3′,5-di-2-propenyl-1,1′-biphenyl-2,4′-diol), an isomer of neolignans isolated and identified from the stem bark of Magnoliaceous plants (Magnolia obovata Thunb, Wa-Koboku in Japanese). The magnolia bark has been utilized as a herbal remedy for the treatment of a wide variety of clinical disorders. Honokiol and magnolol (an isomer of honokiol) were recently identified as anxiolytic agents in the extracts of Saiboku-to, an oriental herbal medicine (Kampo). Behavioral evaluation through an elevated plus-maze test demonstrated that honokiol, 0.2–2 mg/kg, p.o., for 7 days, was at least 5000 times more potent than Saiboku-to. Honokiol has a comparatively lower risk of causing benzodiazepine-like side effects, such as central depression, muscle relaxation, amnesia, or physical dependence. In addition to these central actions, a wide variety of pharmacological effects and biochemical activities of honokiol have been reported during the past 10 years. The main effects, including the limited information regarding the metabolism and kinetics of the compound, are briefly introduced in this text. Information available on honokiol, including its specific and simple chemical structure, suggests the possibility of deriving more potent compounds in the drug design process.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"30 1","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75577672","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.TB00205.X
D. Braida, M. Sala
Eptastigmine (heptyl-physostigmine tartrate) is a carbamate derivative of physostigmine in which the carbamoylmethyl group in position 5 of the side chain has been substituted with a carbamoylheptyl group. In vitro and ex vivo results suggest that eptastigmine has a long-lasting reversible brain cholinesterase (i.e., acetylcholinesterase and butyryl-cholinesterase) inhibitory effect. When administered in vivo to rodents by various routes, eptastigmine inhibits cerebral acetylcholinesterases (AChE) and increases acetylcholine (Ach) brain levels by 2500-3000%, depending on the dose. This effect leads to an improvement in the cerebral blood flow in the ischemic brain, excitatory and inhibitory effects on the gastrointestinal tract and to a protection from acute soman and diisopropylfluorophosphate intoxication. Eptastigmine, by either acute or chronic administration, has been found to have memory enhancing effects in different species of normal, aged and lesioned animals. It also restored to normal the age-related increase of EEG power without affecting spontaneous motor activity. Clinical investigations on more than 1500 patients with Alzheimer's disease demonstrated that eptastigmine significantly improved cognitive performance (as assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale) as compared with placebo. This improvement was most evident in patients with more severe cognitive impairment at the baseline. The relationship between patient performance and average steady-state AChE inhibition was described by an inverted U-shaped dose-response curve. Pharmacokinetic studies have revealed that after oral administration eptastigmine is rapidly distributed to the tissues and readily enters the CNS, where it can be expected to inhibit AChE for a prolonged period. Eptastigmine is generally well tolerated and the majority of adverse events (cholinergic) were mild to moderate in intensity. However, the adverse hematologic (granulocytopenia) effects reported in two studies have resulted in the suspension of further clinical trials.
{"title":"Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and clinical studies.","authors":"D. Braida, M. Sala","doi":"10.1111/J.1527-3458.2001.TB00205.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00205.X","url":null,"abstract":"Eptastigmine (heptyl-physostigmine tartrate) is a carbamate derivative of physostigmine in which the carbamoylmethyl group in position 5 of the side chain has been substituted with a carbamoylheptyl group. In vitro and ex vivo results suggest that eptastigmine has a long-lasting reversible brain cholinesterase (i.e., acetylcholinesterase and butyryl-cholinesterase) inhibitory effect. When administered in vivo to rodents by various routes, eptastigmine inhibits cerebral acetylcholinesterases (AChE) and increases acetylcholine (Ach) brain levels by 2500-3000%, depending on the dose. This effect leads to an improvement in the cerebral blood flow in the ischemic brain, excitatory and inhibitory effects on the gastrointestinal tract and to a protection from acute soman and diisopropylfluorophosphate intoxication. Eptastigmine, by either acute or chronic administration, has been found to have memory enhancing effects in different species of normal, aged and lesioned animals. It also restored to normal the age-related increase of EEG power without affecting spontaneous motor activity. Clinical investigations on more than 1500 patients with Alzheimer's disease demonstrated that eptastigmine significantly improved cognitive performance (as assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale) as compared with placebo. This improvement was most evident in patients with more severe cognitive impairment at the baseline. The relationship between patient performance and average steady-state AChE inhibition was described by an inverted U-shaped dose-response curve. Pharmacokinetic studies have revealed that after oral administration eptastigmine is rapidly distributed to the tissues and readily enters the CNS, where it can be expected to inhibit AChE for a prolonged period. Eptastigmine is generally well tolerated and the majority of adverse events (cholinergic) were mild to moderate in intensity. However, the adverse hematologic (granulocytopenia) effects reported in two studies have resulted in the suspension of further clinical trials.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"60 1","pages":"369-86"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83758228","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}
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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：