Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease
Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase...
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| Veröffentlicht in: | BMC neuroscience 2014-06, Vol.15 (1), p.79-79, Article 79 |
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| creator | Kadoguchi, Naoto Okabe, Shinji Yamamura, Yukio Shono, Misaki Fukano, Tatsuya Tanabe, Akie Yokoyama, Hironori Kasahara, Jiro |
| description | Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.
Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.
Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. |
| doi_str_mv | 10.1186/1471-2202-15-79 |
| format | Article |
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Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.
Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.</description><identifier>ISSN: 1471-2202</identifier><identifier>EISSN: 1471-2202</identifier><identifier>DOI: 10.1186/1471-2202-15-79</identifier><identifier>PMID: 24965042</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Antidepressants ; Antidepressive Agents, Tricyclic - therapeutic use ; Brain - drug effects ; Brain - physiopathology ; Colleges & universities ; Dehydrogenases ; Disease Models, Animal ; Dopamine ; Drug dosages ; Feasibility Studies ; Health aspects ; High performance liquid chromatography ; Male ; Mianserin - analogs & derivatives ; Mianserin - therapeutic use ; Mice ; Mice, Inbred C57BL ; MPTP Poisoning - diagnosis ; MPTP Poisoning - drug therapy ; MPTP Poisoning - physiopathology ; Nassa ; Neurosciences ; Parkinson's disease ; Pharmaceuticals ; Physiological aspects ; Polymerase chain reaction ; Rodents ; Serotonin ; Statistical analysis ; Treatment Outcome ; Variance analysis</subject><ispartof>BMC neuroscience, 2014-06, Vol.15 (1), p.79-79, Article 79</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Kadoguchi et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Kadoguchi et al.; licensee BioMed Central Ltd. 2014 Kadoguchi et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b690t-289e369c6d8e5c80cd66402094c4f130539c834f373edd5f1530e55e4f4333e3</citedby><cites>FETCH-LOGICAL-b690t-289e369c6d8e5c80cd66402094c4f130539c834f373edd5f1530e55e4f4333e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076436/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076436/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24965042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kadoguchi, Naoto</creatorcontrib><creatorcontrib>Okabe, Shinji</creatorcontrib><creatorcontrib>Yamamura, Yukio</creatorcontrib><creatorcontrib>Shono, Misaki</creatorcontrib><creatorcontrib>Fukano, Tatsuya</creatorcontrib><creatorcontrib>Tanabe, Akie</creatorcontrib><creatorcontrib>Yokoyama, Hironori</creatorcontrib><creatorcontrib>Kasahara, Jiro</creatorcontrib><title>Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease</title><title>BMC neuroscience</title><addtitle>BMC Neurosci</addtitle><description>Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.
Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.
Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antidepressants</subject><subject>Antidepressive Agents, Tricyclic - therapeutic use</subject><subject>Brain - drug effects</subject><subject>Brain - physiopathology</subject><subject>Colleges & universities</subject><subject>Dehydrogenases</subject><subject>Disease Models, Animal</subject><subject>Dopamine</subject><subject>Drug dosages</subject><subject>Feasibility Studies</subject><subject>Health aspects</subject><subject>High performance liquid chromatography</subject><subject>Male</subject><subject>Mianserin - analogs & derivatives</subject><subject>Mianserin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MPTP Poisoning - diagnosis</subject><subject>MPTP Poisoning - drug therapy</subject><subject>MPTP Poisoning - physiopathology</subject><subject>Nassa</subject><subject>Neurosciences</subject><subject>Parkinson's disease</subject><subject>Pharmaceuticals</subject><subject>Physiological aspects</subject><subject>Polymerase chain reaction</subject><subject>Rodents</subject><subject>Serotonin</subject><subject>Statistical analysis</subject><subject>Treatment Outcome</subject><subject>Variance analysis</subject><issn>1471-2202</issn><issn>1471-2202</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1Uk1v1DAQjRCIlsKZG7LEgSJtWjv-SHJBKhVfUiv2sHfLa08al8RO7QQp_AB-N462rLqoyLI8mnnzPDNvsuw1wWeEVOKcsJLkRYGLnPC8rJ9kx3vP0wf2UfYixluMSVmx4nl2VLBacMyK4-z3tQ2j-qUG6wC1KiKFxhaCGmAarUaDH8HpGVmHSN7D2M5dzvKhBZcMsipWdCXyEcag2tkEP8zBmoXp9Hq9Wb_PrTOTBoN6qwH13kCHfIPWKvywLnr3LiJjI6gIL7NnjeoivLp_T7LN50-by6_51fcv3y4vrvKtqPGYF1UNVNRamAq4rrA2QjBc4Jpp1hCKOa11RVlDSwrG8IZwioFzYA2jlAI9yT7saIdp24PR4FLlnRyC7VWYpVdWHkacbeWN_ykZLgWjIhF83BFsrf8PwWFE-14uMshFBkm4LOtEcnpfRfB3E8RR9jZq6DrlwE8xoVjSqao5T9C3_0Bv_RRcGtGCSpSUpLtH3agOpHWNT3_rhVRepJFwUdaEJtTZI6h0DCR9vIPGJv9BwvkuQQcfY4Bm3yfBclm_Rzp783C-e_zffaN_AFgK07M</recordid><startdate>20140625</startdate><enddate>20140625</enddate><creator>Kadoguchi, Naoto</creator><creator>Okabe, Shinji</creator><creator>Yamamura, Yukio</creator><creator>Shono, Misaki</creator><creator>Fukano, Tatsuya</creator><creator>Tanabe, Akie</creator><creator>Yokoyama, Hironori</creator><creator>Kasahara, Jiro</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20140625</creationdate><title>Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease</title><author>Kadoguchi, Naoto ; Okabe, Shinji ; Yamamura, Yukio ; Shono, Misaki ; Fukano, Tatsuya ; Tanabe, Akie ; Yokoyama, Hironori ; Kasahara, Jiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b690t-289e369c6d8e5c80cd66402094c4f130539c834f373edd5f1530e55e4f4333e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antidepressants</topic><topic>Antidepressive Agents, Tricyclic - therapeutic use</topic><topic>Brain - drug effects</topic><topic>Brain - physiopathology</topic><topic>Colleges & universities</topic><topic>Dehydrogenases</topic><topic>Disease Models, Animal</topic><topic>Dopamine</topic><topic>Drug dosages</topic><topic>Feasibility Studies</topic><topic>Health aspects</topic><topic>High performance liquid chromatography</topic><topic>Male</topic><topic>Mianserin - analogs & derivatives</topic><topic>Mianserin - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MPTP Poisoning - diagnosis</topic><topic>MPTP Poisoning - drug therapy</topic><topic>MPTP Poisoning - physiopathology</topic><topic>Nassa</topic><topic>Neurosciences</topic><topic>Parkinson's disease</topic><topic>Pharmaceuticals</topic><topic>Physiological aspects</topic><topic>Polymerase chain reaction</topic><topic>Rodents</topic><topic>Serotonin</topic><topic>Statistical analysis</topic><topic>Treatment Outcome</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kadoguchi, Naoto</creatorcontrib><creatorcontrib>Okabe, Shinji</creatorcontrib><creatorcontrib>Yamamura, Yukio</creatorcontrib><creatorcontrib>Shono, Misaki</creatorcontrib><creatorcontrib>Fukano, Tatsuya</creatorcontrib><creatorcontrib>Tanabe, Akie</creatorcontrib><creatorcontrib>Yokoyama, Hironori</creatorcontrib><creatorcontrib>Kasahara, Jiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kadoguchi, Naoto</au><au>Okabe, Shinji</au><au>Yamamura, Yukio</au><au>Shono, Misaki</au><au>Fukano, Tatsuya</au><au>Tanabe, Akie</au><au>Yokoyama, Hironori</au><au>Kasahara, Jiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease</atitle><jtitle>BMC neuroscience</jtitle><addtitle>BMC Neurosci</addtitle><date>2014-06-25</date><risdate>2014</risdate><volume>15</volume><issue>1</issue><spage>79</spage><epage>79</epage><pages>79-79</pages><artnum>79</artnum><issn>1471-2202</issn><eissn>1471-2202</eissn><abstract>Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.
Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.
Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24965042</pmid><doi>10.1186/1471-2202-15-79</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerNature Journals; PubMed Central Open Access; Springer Nature OA Free Journals; PubMed Central |
| subjects | Analysis Animals Antidepressants Antidepressive Agents, Tricyclic - therapeutic use Brain - drug effects Brain - physiopathology Colleges & universities Dehydrogenases Disease Models, Animal Dopamine Drug dosages Feasibility Studies Health aspects High performance liquid chromatography Male Mianserin - analogs & derivatives Mianserin - therapeutic use Mice Mice, Inbred C57BL MPTP Poisoning - diagnosis MPTP Poisoning - drug therapy MPTP Poisoning - physiopathology Nassa Neurosciences Parkinson's disease Pharmaceuticals Physiological aspects Polymerase chain reaction Rodents Serotonin Statistical analysis Treatment Outcome Variance analysis |
| title | Mirtazapine has a therapeutic potency in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease |
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