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Progress in studies of huperzine A,a natural cholinesterase inhibitor from Chinese herbal medicine

Acta Pharmacologica Sinica 2006年第1期27卷 1-26页

作者： Rui WANG Hart YAN Xi-can TANG State Key Lahoratory of Drug Research.Shanghai Institute of Materia Medica.Shanghai Institutes for Biological Sciences Chinese Academy of Sciences.Shanghai 201203,China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Huperzine A (HupA),a novel alkaloid isolated flom the Chinese herb Huperziaserrata,is a potent,highly specific and reversible inhibitor of acetylcholinesterase(ACHE).Compared with tacrine,donepezil,and rivastigmine,HupA has betterpenetration through the blood-brain barrier,higher oral bioavailability,and longerduration of AChE inhibitory *** has been found to improve cognitivedeficits in a broad range of animal *** possesses the ability to protectcells against hydrogen peroxide,β-amyloid protein (or peptide),glutamate,ischemia and staurosporine-induced cytotoxicity and *** protec-tive effects are related to its ability to attenuate oxidative stress,regulate theexpression of apoptotic proteins ***,P53,and caspase-3,protectmitochondria,upregulate nerve growth factor and its receptors,and interfere withamyloid precursor protein *** effects of HupA on N-me-thyl-D-aspartate receptors and potassium currents may also contribute to itsneuroprotection as *** studies in rodents,canines,and healthyhuman volunteers indicated that HupA was absorbed rapidly,distributed widelyin the body,and eliminated at a moderate rate with the property of slow andprolonged release after oral *** and clinical safety tests showedthat HupA had no unexpected toxicity,particularly the dose-limiting hepalotoxic-ity induced by *** phase Ⅳ clinical trials in China have demonstratedthat HupA significantly improved memory deficits in elderly people with benignsenescent forgetfulness,and patients with Alzheimer disease and vasculardementia,with minimal peripheral cholinergic side effects and no *** can also be used as a protective agent against organophosphateintoxication.

关键词： huperzine A Alzheimer disease acetylcholinesterase cholinesterase inhibitors cognitive enhancer neuroprotect agents oxidative stress apoptosis

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Rolipram inhibits the heroin-seeking behavior induced by heroin priming or heroin-associated conditioned cues in rats

Rolipram inhibits the heroin-seeking behavior induced by her...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Miao-Jun LAI~1,Hua-Qiang ZHU~1,Dan FU~1,Wei-Sheng CHENG~1,Han-Ting ZHANG~(2,*),Wen-Hua ZHOU~(1,*) 1 Laboratory of Behavioral Neuroscience,Ningbo Addiction Research and Treatment Center,School of Medicine, Ningbo University,China 2 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology,West Virginia University Health Sciences Center,USA

＜正＞Objective Several lines of evidence have suggested a critical role for CREB activities,which activated by changes of cAMP in mediating the rewarding and reinforcement effects of many drugs of *** of phosphodiesterase（PDE） increase the concentration of cAMP and activate the ***,a cAMP-selective phosphodiesterase 4（PDE4） inhibitor has been thought to enhance the cognitive function,but whether the rolipram inhibit the drug seeking behavior is still *** Our aim was to investigate the effect of rolipram,on cueor heroin-primed heroin-seeking in *** were self-administered heroin for 12 days and extinguished for 12 days, then,conditioned cues or heroin priming（250μg/kg） was introduced for the reinstatement of heroin-seeking behaviors. Results The reinstatement of heroin seeking induced by cues or heroin priming was attenuated by administration of rolipram（0,0.3,1 or 3 mg/kg,i.p.） in a dose-dependent *** pretreatment with rolipram did not inhibit the heroin *** expression of p-CREB in nucleus accumbens was increased when pretreatment with *** The data suggested that rolipram could be used as a potential pharmacotherapeutic agent to reduce drug-seeking.

关键词： cognitive enhancer addiction heroin cAMP

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