Muscarinic agonists and antagonists in the treatment of Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have bee...
Gespeichert in:
| Veröffentlicht in: | Farmaco (Società chimica italiana : 1989) 2001-04, Vol.56 (4), p.247-250 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 250 |
|---|---|
| container_issue | 4 |
| container_start_page | 247 |
| container_title | Farmaco (Società chimica italiana : 1989) |
| container_volume | 56 |
| creator | Greenlee, W Clader, J Asberom, T McCombie, S Ford, J Guzik, H Kozlowski, J Li, S Liu, C Lowe, D Vice, S Zhao, H Zhou, G Billard, W Binch, H Crosby, R Duffy, R Lachowicz, J Coffin, V Watkins, R Ruperto, V Strader, C Taylor, L Cox, K |
| description | Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, galanthamine), limited success has been achieved with direct M
1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M
2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M
2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition. |
| doi_str_mv | 10.1016/S0014-827X(01)01102-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70950380</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014827X01011028</els_id><sourcerecordid>70950380</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-71f349c45b19759d88343e8a644862173ce3c400b844526ea4e65d805f7a48163</originalsourceid><addsrcrecordid>eNqFkEtLHEEQgJugZFeTn6DMQaIeJlbN9GtOYRFNgkoOJpBb09tToy3zWLt7A_rrM-suqzcPRVXBVw8-xg4QviKgPLsFQJ7rQv09ATwFRChy_YFNUasqByGrHTbdIhO2F-PD2Col1Uc2QeQFFgKn7OpmGZ0Nvvcus3dD72OKme3rMdK2932W7ilLgWzqqE_Z0GSz9vmefEfhOGa1j2QjfWK7jW0jfd7kffbn8uL3-Y_8-tf3n-ez69xxIVOusCl5NdZzrJSoaq1LXpK2knMtC1Slo9JxgLnmXBSSLCcpag2iUZZrlOU--7LeuwjD45JiMp2PjtrW9jQso1FQCSg1jKBYgy4MMQZqzCL4zoYng2BWFs2LRbNSZADNi0Wjx7nDzYHlvKP6dWqjbQSONoAd7bVNsL3z8c12AMFXj35bYzTa-OcpmOg89Y5qH8glUw_-nU_-A5LQjQM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70950380</pqid></control><display><type>article</type><title>Muscarinic agonists and antagonists in the treatment of Alzheimer's disease</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Greenlee, W ; Clader, J ; Asberom, T ; McCombie, S ; Ford, J ; Guzik, H ; Kozlowski, J ; Li, S ; Liu, C ; Lowe, D ; Vice, S ; Zhao, H ; Zhou, G ; Billard, W ; Binch, H ; Crosby, R ; Duffy, R ; Lachowicz, J ; Coffin, V ; Watkins, R ; Ruperto, V ; Strader, C ; Taylor, L ; Cox, K</creator><creatorcontrib>Greenlee, W ; Clader, J ; Asberom, T ; McCombie, S ; Ford, J ; Guzik, H ; Kozlowski, J ; Li, S ; Liu, C ; Lowe, D ; Vice, S ; Zhao, H ; Zhou, G ; Billard, W ; Binch, H ; Crosby, R ; Duffy, R ; Lachowicz, J ; Coffin, V ; Watkins, R ; Ruperto, V ; Strader, C ; Taylor, L ; Cox, K</creatorcontrib><description>Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, galanthamine), limited success has been achieved with direct M
1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M
2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M
2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.</description><identifier>ISSN: 0014-827X</identifier><identifier>EISSN: 1879-0569</identifier><identifier>DOI: 10.1016/S0014-827X(01)01102-8</identifier><identifier>PMID: 11421251</identifier><language>eng</language><publisher>Lausanne: Elsevier SAS</publisher><subject>Alzheimer Disease - drug therapy ; Alzheimer's disease ; Animals ; Biological and medical sciences ; Cholinergic ; Cholinergic system ; Humans ; M 2 Receptors ; Medical sciences ; Muscarinic ; Muscarinic Agonists - chemistry ; Muscarinic Agonists - therapeutic use ; Muscarinic Antagonists - chemistry ; Muscarinic Antagonists - therapeutic use ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Structure-Activity Relationship</subject><ispartof>Farmaco (Società chimica italiana : 1989), 2001-04, Vol.56 (4), p.247-250</ispartof><rights>2001 Elsevier Science S.A.</rights><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-71f349c45b19759d88343e8a644862173ce3c400b844526ea4e65d805f7a48163</citedby><cites>FETCH-LOGICAL-c456t-71f349c45b19759d88343e8a644862173ce3c400b844526ea4e65d805f7a48163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1000546$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11421251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Greenlee, W</creatorcontrib><creatorcontrib>Clader, J</creatorcontrib><creatorcontrib>Asberom, T</creatorcontrib><creatorcontrib>McCombie, S</creatorcontrib><creatorcontrib>Ford, J</creatorcontrib><creatorcontrib>Guzik, H</creatorcontrib><creatorcontrib>Kozlowski, J</creatorcontrib><creatorcontrib>Li, S</creatorcontrib><creatorcontrib>Liu, C</creatorcontrib><creatorcontrib>Lowe, D</creatorcontrib><creatorcontrib>Vice, S</creatorcontrib><creatorcontrib>Zhao, H</creatorcontrib><creatorcontrib>Zhou, G</creatorcontrib><creatorcontrib>Billard, W</creatorcontrib><creatorcontrib>Binch, H</creatorcontrib><creatorcontrib>Crosby, R</creatorcontrib><creatorcontrib>Duffy, R</creatorcontrib><creatorcontrib>Lachowicz, J</creatorcontrib><creatorcontrib>Coffin, V</creatorcontrib><creatorcontrib>Watkins, R</creatorcontrib><creatorcontrib>Ruperto, V</creatorcontrib><creatorcontrib>Strader, C</creatorcontrib><creatorcontrib>Taylor, L</creatorcontrib><creatorcontrib>Cox, K</creatorcontrib><title>Muscarinic agonists and antagonists in the treatment of Alzheimer's disease</title><title>Farmaco (Società chimica italiana : 1989)</title><addtitle>Farmaco</addtitle><description>Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, galanthamine), limited success has been achieved with direct M
1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M
2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M
2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cholinergic</subject><subject>Cholinergic system</subject><subject>Humans</subject><subject>M 2 Receptors</subject><subject>Medical sciences</subject><subject>Muscarinic</subject><subject>Muscarinic Agonists - chemistry</subject><subject>Muscarinic Agonists - therapeutic use</subject><subject>Muscarinic Antagonists - chemistry</subject><subject>Muscarinic Antagonists - therapeutic use</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Structure-Activity Relationship</subject><issn>0014-827X</issn><issn>1879-0569</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLHEEQgJugZFeTn6DMQaIeJlbN9GtOYRFNgkoOJpBb09tToy3zWLt7A_rrM-suqzcPRVXBVw8-xg4QviKgPLsFQJ7rQv09ATwFRChy_YFNUasqByGrHTbdIhO2F-PD2Col1Uc2QeQFFgKn7OpmGZ0Nvvcus3dD72OKme3rMdK2932W7ilLgWzqqE_Z0GSz9vmefEfhOGa1j2QjfWK7jW0jfd7kffbn8uL3-Y_8-tf3n-ez69xxIVOusCl5NdZzrJSoaq1LXpK2knMtC1Slo9JxgLnmXBSSLCcpag2iUZZrlOU--7LeuwjD45JiMp2PjtrW9jQso1FQCSg1jKBYgy4MMQZqzCL4zoYng2BWFs2LRbNSZADNi0Wjx7nDzYHlvKP6dWqjbQSONoAd7bVNsL3z8c12AMFXj35bYzTa-OcpmOg89Y5qH8glUw_-nU_-A5LQjQM</recordid><startdate>20010401</startdate><enddate>20010401</enddate><creator>Greenlee, W</creator><creator>Clader, J</creator><creator>Asberom, T</creator><creator>McCombie, S</creator><creator>Ford, J</creator><creator>Guzik, H</creator><creator>Kozlowski, J</creator><creator>Li, S</creator><creator>Liu, C</creator><creator>Lowe, D</creator><creator>Vice, S</creator><creator>Zhao, H</creator><creator>Zhou, G</creator><creator>Billard, W</creator><creator>Binch, H</creator><creator>Crosby, R</creator><creator>Duffy, R</creator><creator>Lachowicz, J</creator><creator>Coffin, V</creator><creator>Watkins, R</creator><creator>Ruperto, V</creator><creator>Strader, C</creator><creator>Taylor, L</creator><creator>Cox, K</creator><general>Elsevier SAS</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20010401</creationdate><title>Muscarinic agonists and antagonists in the treatment of Alzheimer's disease</title><author>Greenlee, W ; Clader, J ; Asberom, T ; McCombie, S ; Ford, J ; Guzik, H ; Kozlowski, J ; Li, S ; Liu, C ; Lowe, D ; Vice, S ; Zhao, H ; Zhou, G ; Billard, W ; Binch, H ; Crosby, R ; Duffy, R ; Lachowicz, J ; Coffin, V ; Watkins, R ; Ruperto, V ; Strader, C ; Taylor, L ; Cox, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-71f349c45b19759d88343e8a644862173ce3c400b844526ea4e65d805f7a48163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cholinergic</topic><topic>Cholinergic system</topic><topic>Humans</topic><topic>M 2 Receptors</topic><topic>Medical sciences</topic><topic>Muscarinic</topic><topic>Muscarinic Agonists - chemistry</topic><topic>Muscarinic Agonists - therapeutic use</topic><topic>Muscarinic Antagonists - chemistry</topic><topic>Muscarinic Antagonists - therapeutic use</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Greenlee, W</creatorcontrib><creatorcontrib>Clader, J</creatorcontrib><creatorcontrib>Asberom, T</creatorcontrib><creatorcontrib>McCombie, S</creatorcontrib><creatorcontrib>Ford, J</creatorcontrib><creatorcontrib>Guzik, H</creatorcontrib><creatorcontrib>Kozlowski, J</creatorcontrib><creatorcontrib>Li, S</creatorcontrib><creatorcontrib>Liu, C</creatorcontrib><creatorcontrib>Lowe, D</creatorcontrib><creatorcontrib>Vice, S</creatorcontrib><creatorcontrib>Zhao, H</creatorcontrib><creatorcontrib>Zhou, G</creatorcontrib><creatorcontrib>Billard, W</creatorcontrib><creatorcontrib>Binch, H</creatorcontrib><creatorcontrib>Crosby, R</creatorcontrib><creatorcontrib>Duffy, R</creatorcontrib><creatorcontrib>Lachowicz, J</creatorcontrib><creatorcontrib>Coffin, V</creatorcontrib><creatorcontrib>Watkins, R</creatorcontrib><creatorcontrib>Ruperto, V</creatorcontrib><creatorcontrib>Strader, C</creatorcontrib><creatorcontrib>Taylor, L</creatorcontrib><creatorcontrib>Cox, K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Farmaco (Società chimica italiana : 1989)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Greenlee, W</au><au>Clader, J</au><au>Asberom, T</au><au>McCombie, S</au><au>Ford, J</au><au>Guzik, H</au><au>Kozlowski, J</au><au>Li, S</au><au>Liu, C</au><au>Lowe, D</au><au>Vice, S</au><au>Zhao, H</au><au>Zhou, G</au><au>Billard, W</au><au>Binch, H</au><au>Crosby, R</au><au>Duffy, R</au><au>Lachowicz, J</au><au>Coffin, V</au><au>Watkins, R</au><au>Ruperto, V</au><au>Strader, C</au><au>Taylor, L</au><au>Cox, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Muscarinic agonists and antagonists in the treatment of Alzheimer's disease</atitle><jtitle>Farmaco (Società chimica italiana : 1989)</jtitle><addtitle>Farmaco</addtitle><date>2001-04-01</date><risdate>2001</risdate><volume>56</volume><issue>4</issue><spage>247</spage><epage>250</epage><pages>247-250</pages><issn>0014-827X</issn><eissn>1879-0569</eissn><abstract>Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil, rivastigmine, galanthamine), limited success has been achieved with direct M
1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M
2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M
2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.</abstract><cop>Lausanne</cop><pub>Elsevier SAS</pub><pmid>11421251</pmid><doi>10.1016/S0014-827X(01)01102-8</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-827X |
| ispartof | Farmaco (Società chimica italiana : 1989), 2001-04, Vol.56 (4), p.247-250 |
| issn | 0014-827X 1879-0569 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70950380 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Alzheimer Disease - drug therapy Alzheimer's disease Animals Biological and medical sciences Cholinergic Cholinergic system Humans M 2 Receptors Medical sciences Muscarinic Muscarinic Agonists - chemistry Muscarinic Agonists - therapeutic use Muscarinic Antagonists - chemistry Muscarinic Antagonists - therapeutic use Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Structure-Activity Relationship |
| title | Muscarinic agonists and antagonists in the treatment of Alzheimer's disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T02%3A30%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Muscarinic%20agonists%20and%20antagonists%20in%20the%20treatment%20of%20Alzheimer's%20disease&rft.jtitle=Farmaco%20(Societ%C3%A0%20chimica%20italiana%20:%201989)&rft.au=Greenlee,%20W&rft.date=2001-04-01&rft.volume=56&rft.issue=4&rft.spage=247&rft.epage=250&rft.pages=247-250&rft.issn=0014-827X&rft.eissn=1879-0569&rft_id=info:doi/10.1016/S0014-827X(01)01102-8&rft_dat=%3Cproquest_cross%3E70950380%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70950380&rft_id=info:pmid/11421251&rft_els_id=S0014827X01011028&rfr_iscdi=true |