Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues
ABSTRACT Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea‐pigs resulted in an average delivery of 1.185 mg selegiline/cm2 pa...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2003-01, Vol.55 (1), p.27-34 |
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| container_title | Journal of pharmacy and pharmacology |
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| creator | Mawhinney, Michael Cole, Dennis Azzaro, Albert J. |
| description | ABSTRACT
Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea‐pigs resulted in an average delivery of 1.185 mg selegiline/cm2 patch/24 h. STS dose‐response curves were generated by altering patch size (cm2). A transdermal dose range was identified which inhibited guinea‐pig brain monoamine oxidase‐B (MAO‐B) by greater than 95 % yet provided for a dose‐dependent inhibition of monoamine oxidase‐A (MAO‐A) activity. The ID50 for inhibition of MAO‐A activity in response to a 21‐day daily regimen with transdermal selegiline was approximately 7.5‐fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO‐A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO‐A to the same extent, and generated a shallower dose–inhibition curve for brain MAO‐A inhibition. In addition, transdermal delivery was approximately 6–8‐times more potent than oral selegiline for the inhibition of brain MAO‐A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose‐dependent inhibition of brain vs peripheral MAO‐A activity. |
| doi_str_mv | 10.1111/j.2042-7158.2003.tb02430.x |
| format | Article |
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Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea‐pigs resulted in an average delivery of 1.185 mg selegiline/cm2 patch/24 h. STS dose‐response curves were generated by altering patch size (cm2). A transdermal dose range was identified which inhibited guinea‐pig brain monoamine oxidase‐B (MAO‐B) by greater than 95 % yet provided for a dose‐dependent inhibition of monoamine oxidase‐A (MAO‐A) activity. The ID50 for inhibition of MAO‐A activity in response to a 21‐day daily regimen with transdermal selegiline was approximately 7.5‐fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO‐A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO‐A to the same extent, and generated a shallower dose–inhibition curve for brain MAO‐A inhibition. In addition, transdermal delivery was approximately 6–8‐times more potent than oral selegiline for the inhibition of brain MAO‐A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose‐dependent inhibition of brain vs peripheral MAO‐A activity.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1111/j.2042-7158.2003.tb02430.x</identifier><identifier>PMID: 12625864</identifier><identifier>CODEN: JPPMAB</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Administration, Cutaneous ; Animals ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Brain - enzymology ; Digestive System - enzymology ; Guinea Pigs ; Liver - enzymology ; Male ; Medical sciences ; Monoamine Oxidase - analysis ; Monoamine Oxidase - pharmacology ; Monoamine Oxidase Inhibitors - administration & dosage ; Monoamine Oxidase Inhibitors - pharmacokinetics ; Monoamine Oxidase Inhibitors - pharmacology ; Neuropharmacology ; Pharmacology. Drug treatments ; Selegiline - administration & dosage ; Selegiline - pharmacokinetics ; Selegiline - pharmacology</subject><ispartof>Journal of pharmacy and pharmacology, 2003-01, Vol.55 (1), p.27-34</ispartof><rights>2003 Royal Pharmaceutical Society of Great Britain</rights><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4240-4d6b1d092895091c7ca1d0508b4466ce379539ab1e87acd8920ad888d54f9ac53</citedby><cites>FETCH-LOGICAL-c4240-4d6b1d092895091c7ca1d0508b4466ce379539ab1e87acd8920ad888d54f9ac53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.2042-7158.2003.tb02430.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.2042-7158.2003.tb02430.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,4021,27921,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14452213$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12625864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mawhinney, Michael</creatorcontrib><creatorcontrib>Cole, Dennis</creatorcontrib><creatorcontrib>Azzaro, Albert J.</creatorcontrib><title>Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>ABSTRACT
Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea‐pigs resulted in an average delivery of 1.185 mg selegiline/cm2 patch/24 h. STS dose‐response curves were generated by altering patch size (cm2). A transdermal dose range was identified which inhibited guinea‐pig brain monoamine oxidase‐B (MAO‐B) by greater than 95 % yet provided for a dose‐dependent inhibition of monoamine oxidase‐A (MAO‐A) activity. The ID50 for inhibition of MAO‐A activity in response to a 21‐day daily regimen with transdermal selegiline was approximately 7.5‐fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO‐A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO‐A to the same extent, and generated a shallower dose–inhibition curve for brain MAO‐A inhibition. In addition, transdermal delivery was approximately 6–8‐times more potent than oral selegiline for the inhibition of brain MAO‐A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose‐dependent inhibition of brain vs peripheral MAO‐A activity.</description><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Brain - enzymology</subject><subject>Digestive System - enzymology</subject><subject>Guinea Pigs</subject><subject>Liver - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Monoamine Oxidase - analysis</subject><subject>Monoamine Oxidase - pharmacology</subject><subject>Monoamine Oxidase Inhibitors - administration & dosage</subject><subject>Monoamine Oxidase Inhibitors - pharmacokinetics</subject><subject>Monoamine Oxidase Inhibitors - pharmacology</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Selegiline - administration & dosage</subject><subject>Selegiline - pharmacokinetics</subject><subject>Selegiline - pharmacology</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkc9uEzEQxlcIRNPCKyALCW4bvLb3HydQS1NQBD0UgbhYs7aTTNj1LrbTJM_ES-JVVu0ZH-yx55tvRv4lyeuMzrO43m3njAqWlllexYjyeWgoE5zOD0-S2UPqaTKjlLGU5yU_S86931JKy6IonidnGStYXhVilvy9AmyPJDiwXhvXQUtAd2jRx6eAvSX9injTmjW2aA0JPVnvYgDpgGtPBmdWxhkbENpog3aDDQZPut720I0F_QE1eENABbzHMGpI4yDu-42xRPXdAM5ossewiblgfEA7TmE12ZghzqBIQO93xr9Inq2g9ebldF4k368_3V3epMtvi8-XH5epEkzQVOiiyTStWVXntM5UqSBec1o1QhSFMrysc15Dk5mqBKWrmlHQVVXpXKxqUDm_SN6efAfX_4l9g-zQK9O2YE2_87LktCo5L6Lw_UmoXO99_Ao5OOzAHWVG5YhKbuXIQ4485IhKTqjkIRa_mrrsms7ox9KJTRS8mQTgFbSriEihf9QJkTOW8aj7cNLtsTXH_xhBfrm9uR3DaJGeLCJ2c3iwAPdbFiUvc_nj60Iuru5-LevlT3nN_wGtPMVg</recordid><startdate>200301</startdate><enddate>200301</enddate><creator>Mawhinney, Michael</creator><creator>Cole, Dennis</creator><creator>Azzaro, Albert J.</creator><general>Blackwell Publishing Ltd</general><general>Pharmaceutical Press</general><scope>BSCLL</scope><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>200301</creationdate><title>Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues</title><author>Mawhinney, Michael ; Cole, Dennis ; Azzaro, Albert J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4240-4d6b1d092895091c7ca1d0508b4466ce379539ab1e87acd8920ad888d54f9ac53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Administration, Cutaneous</topic><topic>Animals</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Brain - enzymology</topic><topic>Digestive System - enzymology</topic><topic>Guinea Pigs</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Monoamine Oxidase - analysis</topic><topic>Monoamine Oxidase - pharmacology</topic><topic>Monoamine Oxidase Inhibitors - administration & dosage</topic><topic>Monoamine Oxidase Inhibitors - pharmacokinetics</topic><topic>Monoamine Oxidase Inhibitors - pharmacology</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Selegiline - administration & dosage</topic><topic>Selegiline - pharmacokinetics</topic><topic>Selegiline - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mawhinney, Michael</creatorcontrib><creatorcontrib>Cole, Dennis</creatorcontrib><creatorcontrib>Azzaro, Albert J.</creatorcontrib><collection>Istex</collection><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>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mawhinney, Michael</au><au>Cole, Dennis</au><au>Azzaro, Albert J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2003-01</date><risdate>2003</risdate><volume>55</volume><issue>1</issue><spage>27</spage><epage>34</epage><pages>27-34</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><coden>JPPMAB</coden><abstract>ABSTRACT
Selegiline has been formulated in an acrylic polymer adhesive mixture to be employed as a constant release topical patch for daily transdermal administration. Application of this selegiline transdermal system (STS) to guinea‐pigs resulted in an average delivery of 1.185 mg selegiline/cm2 patch/24 h. STS dose‐response curves were generated by altering patch size (cm2). A transdermal dose range was identified which inhibited guinea‐pig brain monoamine oxidase‐B (MAO‐B) by greater than 95 % yet provided for a dose‐dependent inhibition of monoamine oxidase‐A (MAO‐A) activity. The ID50 for inhibition of MAO‐A activity in response to a 21‐day daily regimen with transdermal selegiline was approximately 7.5‐fold lower for cortical and striatal brain regions compared with that obtained for duodenum; hepatic MAO‐A was unaffected following the same dosing regimen. By contrast, orally administered selegiline inhibited brain and duodenal MAO‐A to the same extent, and generated a shallower dose–inhibition curve for brain MAO‐A inhibition. In addition, transdermal delivery was approximately 6–8‐times more potent than oral selegiline for the inhibition of brain MAO‐A activity. It is concluded that daily transdermal selegiline administration may provide therapeutic advantages over oral treatment, based on its preferential, dose‐dependent inhibition of brain vs peripheral MAO‐A activity.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>12625864</pmid><doi>10.1111/j.2042-7158.2003.tb02430.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of pharmacy and pharmacology, 2003-01, Vol.55 (1), p.27-34 |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Administration, Cutaneous Animals Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Brain - enzymology Digestive System - enzymology Guinea Pigs Liver - enzymology Male Medical sciences Monoamine Oxidase - analysis Monoamine Oxidase - pharmacology Monoamine Oxidase Inhibitors - administration & dosage Monoamine Oxidase Inhibitors - pharmacokinetics Monoamine Oxidase Inhibitors - pharmacology Neuropharmacology Pharmacology. Drug treatments Selegiline - administration & dosage Selegiline - pharmacokinetics Selegiline - pharmacology |
| title | Daily transdermal administration of selegiline to guinea-pigs preferentially inhibits monoamine oxidase activity in brain when compared with intestinal and hepatic tissues |
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