Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats : comparison with CPPene
Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed a...
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| Veröffentlicht in: | Neuropharmacology 1993, Vol.32 (1), p.51-58 |
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| creator | DE SARRO, G. B DE SARRO, A |
| description | Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure. The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested. |
| doi_str_mv | 10.1016/0028-3908(93)90129-Q |
| format | Article |
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B ; DE SARRO, A</creator><creatorcontrib>DE SARRO, G. B ; DE SARRO, A</creatorcontrib><description>Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure. The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/0028-3908(93)90129-Q</identifier><identifier>PMID: 8094234</identifier><identifier>CODEN: NEPHBW</identifier><language>eng</language><publisher>Oxford: Elsevier</publisher><subject>Acoustic Stimulation ; Adrenergic alpha-Antagonists - pharmacology ; Adrenergic alpha-Antagonists - toxicity ; Animals ; Anticonvulsants - pharmacology ; Anticonvulsants - toxicity ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Dextromethorphan - pharmacology ; Dextromethorphan - toxicity ; Dizocilpine Maleate - pharmacology ; Dizocilpine Maleate - toxicity ; Epilepsy - genetics ; Epilepsy - prevention & control ; Injections, Intraperitoneal ; Ketamine - pharmacology ; Ketamine - toxicity ; Male ; Medical sciences ; Movement - drug effects ; Neuropharmacology ; Pharmacology. Drug treatments ; Phencyclidine - pharmacology ; Phencyclidine - toxicity ; Piperazines - pharmacology ; Piperazines - toxicity ; Piperidines - pharmacology ; Piperidines - toxicity ; Postural Balance - drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><ispartof>Neuropharmacology, 1993, Vol.32 (1), p.51-58</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c277t-e29ba574d77d14ea5566634691fac116cbe262b7f273beba3a7bec3adc3c913e3</citedby><cites>FETCH-LOGICAL-c277t-e29ba574d77d14ea5566634691fac116cbe262b7f273beba3a7bec3adc3c913e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,4025,27928,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4524614$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8094234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DE SARRO, G. B</creatorcontrib><creatorcontrib>DE SARRO, A</creatorcontrib><title>Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats : comparison with CPPene</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure. The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested.</description><subject>Acoustic Stimulation</subject><subject>Adrenergic alpha-Antagonists - pharmacology</subject><subject>Adrenergic alpha-Antagonists - toxicity</subject><subject>Animals</subject><subject>Anticonvulsants - pharmacology</subject><subject>Anticonvulsants - toxicity</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Dextromethorphan - pharmacology</subject><subject>Dextromethorphan - toxicity</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Dizocilpine Maleate - toxicity</subject><subject>Epilepsy - genetics</subject><subject>Epilepsy - prevention & control</subject><subject>Injections, Intraperitoneal</subject><subject>Ketamine - pharmacology</subject><subject>Ketamine - toxicity</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Movement - drug effects</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phencyclidine - pharmacology</subject><subject>Phencyclidine - toxicity</subject><subject>Piperazines - pharmacology</subject><subject>Piperazines - toxicity</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - toxicity</subject><subject>Postural Balance - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kc1uEzEUhS0EKqHwBiB5gRAsDP4be8yuCr9SBa0Ea8vj3GmMZuyp7RTlUXhbnDbKyovznXOtcxB6yeh7Rpn6QCnviTC0f2vEO0MZN-T6EVqxXguiqZKP0eqEPEXPSvlDKZU968_QWU-N5EKu0L-LWINP8W43FRcrXnJaINcABacRxxSJT_MCNdRwB7gR7ibFUOq9XLeAf5AZ6nY_kU_ElcXl6irgDB6WmjIOEd9AbHbvpmmPYQkTLGVP2pnYMNdyPuLDBZdDSRH_DXWL11dXzfMcPRndVODF8T1Hv798_rX-Ri5_fv2-vrgknmtdCXAzuE7LjdYbJsF1nVJKSGXY6Dxjyg_AFR_0yLUYYHDC6QG8cBsvvGECxDl685Db_nS7g1LtHIqHaXIR0q5YpjrWacYbKB9An1MpGUa75DC7vLeM2sMi9lC3PdRtjbD3i9jrZnt1zN8NM2xOpuMETX991F1pLY3ZRR_KCZMdl4pJ8R_Xapfr</recordid><startdate>1993</startdate><enddate>1993</enddate><creator>DE SARRO, G. B</creator><creator>DE SARRO, A</creator><general>Elsevier</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>7TK</scope></search><sort><creationdate>1993</creationdate><title>Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats : comparison with CPPene</title><author>DE SARRO, G. B ; DE SARRO, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c277t-e29ba574d77d14ea5566634691fac116cbe262b7f273beba3a7bec3adc3c913e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Acoustic Stimulation</topic><topic>Adrenergic alpha-Antagonists - pharmacology</topic><topic>Adrenergic alpha-Antagonists - toxicity</topic><topic>Animals</topic><topic>Anticonvulsants - pharmacology</topic><topic>Anticonvulsants - toxicity</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Dextromethorphan - pharmacology</topic><topic>Dextromethorphan - toxicity</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Dizocilpine Maleate - toxicity</topic><topic>Epilepsy - genetics</topic><topic>Epilepsy - prevention & control</topic><topic>Injections, Intraperitoneal</topic><topic>Ketamine - pharmacology</topic><topic>Ketamine - toxicity</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Movement - drug effects</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phencyclidine - pharmacology</topic><topic>Phencyclidine - toxicity</topic><topic>Piperazines - pharmacology</topic><topic>Piperazines - toxicity</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - toxicity</topic><topic>Postural Balance - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DE SARRO, G. B</creatorcontrib><creatorcontrib>DE SARRO, A</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>Neurosciences Abstracts</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DE SARRO, G. B</au><au>DE SARRO, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats : comparison with CPPene</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>1993</date><risdate>1993</risdate><volume>32</volume><issue>1</issue><spage>51</spage><epage>58</epage><pages>51-58</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><coden>NEPHBW</coden><abstract>Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure. The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested.</abstract><cop>Oxford</cop><pub>Elsevier</pub><pmid>8094234</pmid><doi>10.1016/0028-3908(93)90129-Q</doi><tpages>8</tpages></addata></record> |
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| ispartof | Neuropharmacology, 1993, Vol.32 (1), p.51-58 |
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| subjects | Acoustic Stimulation Adrenergic alpha-Antagonists - pharmacology Adrenergic alpha-Antagonists - toxicity Animals Anticonvulsants - pharmacology Anticonvulsants - toxicity Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Dextromethorphan - pharmacology Dextromethorphan - toxicity Dizocilpine Maleate - pharmacology Dizocilpine Maleate - toxicity Epilepsy - genetics Epilepsy - prevention & control Injections, Intraperitoneal Ketamine - pharmacology Ketamine - toxicity Male Medical sciences Movement - drug effects Neuropharmacology Pharmacology. Drug treatments Phencyclidine - pharmacology Phencyclidine - toxicity Piperazines - pharmacology Piperazines - toxicity Piperidines - pharmacology Piperidines - toxicity Postural Balance - drug effects Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors |
| title | Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats : comparison with CPPene |
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