Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus
1 The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chem...
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| Veröffentlicht in: | British journal of pharmacology 1986-05, Vol.88 (1), p.285-290 |
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| creator | Dougan, D.F.H. Duffield, A.M. Duffield, P.H. Wade, D.N. |
| description | 1
The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.).
2
Two h after the administration of (+)‐ or (−)‐AMPT (5 mg kg−1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)‐isomer was 10 times that of the (−)‐isomer.
3
The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)‐AMPT were 68 ng g−1 and 484 ng g−1 respectively. After the administration of the (−)‐isomer of AMPT, small quantities of AMPO were detected in both brain areas.
4
Twenty h after the last of 7 daily injections of (+)‐Amphet (5 mg kg−1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5.
5
These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)‐isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals.
6
The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half‐lives of (+)‐AMPT and (+)‐AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half‐life for hypothalamic (+)‐AMPO was 7 days.
7
These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970). |
| doi_str_mv | 10.1111/j.1476-5381.1986.tb09497.x |
| format | Article |
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The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.).
2
Two h after the administration of (+)‐ or (−)‐AMPT (5 mg kg−1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)‐isomer was 10 times that of the (−)‐isomer.
3
The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)‐AMPT were 68 ng g−1 and 484 ng g−1 respectively. After the administration of the (−)‐isomer of AMPT, small quantities of AMPO were detected in both brain areas.
4
Twenty h after the last of 7 daily injections of (+)‐Amphet (5 mg kg−1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5.
5
These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)‐isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals.
6
The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half‐lives of (+)‐AMPT and (+)‐AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half‐life for hypothalamic (+)‐AMPO was 7 days.
7
These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970).</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.1986.tb09497.x</identifier><identifier>PMID: 3708221</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Amphetamine - metabolism ; Amphetamine - pharmacology ; Animals ; Benzyl Compounds - metabolism ; Biological and medical sciences ; Corpus Striatum - metabolism ; Half-Life ; Hydroxylation ; Hypothalamus - metabolism ; Male ; Medical sciences ; Neuropharmacology ; Octopamine - analogs & derivatives ; Pharmacology. Drug treatments ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Rats ; Stereoisomerism ; Tyramine - analogs & derivatives ; Tyramine - metabolism ; Tyramine - pharmacology</subject><ispartof>British journal of pharmacology, 1986-05, Vol.88 (1), p.285-290</ispartof><rights>1986 British Pharmacological Society</rights><rights>1987 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5377-e5d409acf33375f802ffa5abe2bdd0f71513503266981d63fb6ceb19d8b826ca3</citedby><cites>FETCH-LOGICAL-c5377-e5d409acf33375f802ffa5abe2bdd0f71513503266981d63fb6ceb19d8b826ca3</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/PMC1917092/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1917092/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8062498$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3708221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dougan, D.F.H.</creatorcontrib><creatorcontrib>Duffield, A.M.</creatorcontrib><creatorcontrib>Duffield, P.H.</creatorcontrib><creatorcontrib>Wade, D.N.</creatorcontrib><title>Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>1
The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.).
2
Two h after the administration of (+)‐ or (−)‐AMPT (5 mg kg−1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)‐isomer was 10 times that of the (−)‐isomer.
3
The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)‐AMPT were 68 ng g−1 and 484 ng g−1 respectively. After the administration of the (−)‐isomer of AMPT, small quantities of AMPO were detected in both brain areas.
4
Twenty h after the last of 7 daily injections of (+)‐Amphet (5 mg kg−1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5.
5
These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)‐isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals.
6
The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half‐lives of (+)‐AMPT and (+)‐AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half‐life for hypothalamic (+)‐AMPO was 7 days.
7
These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970).</description><subject>Amphetamine - metabolism</subject><subject>Amphetamine - pharmacology</subject><subject>Animals</subject><subject>Benzyl Compounds - metabolism</subject><subject>Biological and medical sciences</subject><subject>Corpus Striatum - metabolism</subject><subject>Half-Life</subject><subject>Hydroxylation</subject><subject>Hypothalamus - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>Octopamine - analogs & derivatives</subject><subject>Pharmacology. Drug treatments</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Rats</subject><subject>Stereoisomerism</subject><subject>Tyramine - analogs & derivatives</subject><subject>Tyramine - metabolism</subject><subject>Tyramine - pharmacology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkV-L1DAUxYMo67j6EYQi4ltr0rT544Oiy64rLCioz-E2TZ0MaTMm6Trz7U2ZMuiTmJeEe849nPBD6AXBFcnn9a4iDWdlSwWpiBSsSh2WjeTV4QHanKWHaIMx5iUhQjxGT2LcYZxF3l6gC8qxqGuyQduvyQTjo3FGJ3tvCtB6HmcHyfqp8EOxPfbBH455YPpiNAk672wycdFg3G_zZLSTKexUBEhFTMFCmscCpj7v7n3agoNxjk_RowFcNM_W-xJ9v7n-dnVb3n3--Onq_V2pW8p5adq-wRL0QCnl7SBwPQzQQmfqru_xwElLaItpzZgUpGd06Jg2HZG96ETNNNBL9PaUu5-70fTaTCmAU_tgRwhH5cGqv5XJbtUPf6-IJBzLOge8WgOC_zmbmNRoozbOwWT8HBVnosEs1_uXkTSNbEhNsvHNyaiDjzGY4dyGYLUAVTu1UFMLNbUAVStQdcjLz__8z3l1JZj1l6sOUYMbAkzaxrNNYFY3UmTbu5Ptl3Xm-B8F1Icvt8uL_gbJlsHD</recordid><startdate>198605</startdate><enddate>198605</enddate><creator>Dougan, D.F.H.</creator><creator>Duffield, A.M.</creator><creator>Duffield, P.H.</creator><creator>Wade, D.N.</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>198605</creationdate><title>Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus</title><author>Dougan, D.F.H. ; Duffield, A.M. ; Duffield, P.H. ; Wade, D.N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5377-e5d409acf33375f802ffa5abe2bdd0f71513503266981d63fb6ceb19d8b826ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Amphetamine - metabolism</topic><topic>Amphetamine - pharmacology</topic><topic>Animals</topic><topic>Benzyl Compounds - metabolism</topic><topic>Biological and medical sciences</topic><topic>Corpus Striatum - metabolism</topic><topic>Half-Life</topic><topic>Hydroxylation</topic><topic>Hypothalamus - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>Octopamine - analogs & derivatives</topic><topic>Pharmacology. Drug treatments</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Rats</topic><topic>Stereoisomerism</topic><topic>Tyramine - analogs & derivatives</topic><topic>Tyramine - metabolism</topic><topic>Tyramine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dougan, D.F.H.</creatorcontrib><creatorcontrib>Duffield, A.M.</creatorcontrib><creatorcontrib>Duffield, P.H.</creatorcontrib><creatorcontrib>Wade, D.N.</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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dougan, D.F.H.</au><au>Duffield, A.M.</au><au>Duffield, P.H.</au><au>Wade, D.N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1986-05</date><risdate>1986</risdate><volume>88</volume><issue>1</issue><spage>285</spage><epage>290</epage><pages>285-290</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>1
The stereoselective accumulation of α‐methyl‐p‐tyramine (AMPT) and α‐methyl‐p‐octopamine (AMPO) in rat striatum and hypothalamus after acute and chronic administration of the (+)‐and (−)‐isomers of amphetamine (Amphet) and the acute administration of (+)‐ and (−)‐AMPT has been investigated by chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.).
2
Two h after the administration of (+)‐ or (−)‐AMPT (5 mg kg−1 i.p.), the concentrations of the isomers in striatal tissue were approximately equal; 18 h later, the concentration of the (+)‐isomer was 10 times that of the (−)‐isomer.
3
The concentrations of AMPO in the striatum and hypothalamus 20 h after administration of (+)‐AMPT were 68 ng g−1 and 484 ng g−1 respectively. After the administration of the (−)‐isomer of AMPT, small quantities of AMPO were detected in both brain areas.
4
Twenty h after the last of 7 daily injections of (+)‐Amphet (5 mg kg−1, i.p.), the concentration of AMPO in the hypothalamus was 5.4 times the concentration at 20 h after one injection. In the striatum, the corresponding ratio for AMPO was 3.5 and for AMPT was 2.5.
5
These data indicate that, although both isomers of AMPT formed from Amphet administered systemically, cross the blood brain barrier, the (+)‐isomers AMPT and AMPO are preferentially stored in striatal and hypothalamic aminergic nerve terminals.
6
The accumulations of AMPT and AMPO in rat striatum and hypothalamus after chronic administration of Amphet demonstrates that these metabolites persist in neuronal storage in these brain areas for days after administration. The half‐lives of (+)‐AMPT and (+)‐AMPO in striatal neuronal storage, calculated from this data, were 1.5 days and 2.5 days, respectively. The corresponding half‐life for hypothalamic (+)‐AMPO was 7 days.
7
These findings suggest the involvement of accumulated AMPT and AMPO in the development of behavioural augmentation to repeated injections of Amphet (Randrup & Munkvad, 1970).</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>3708221</pmid><doi>10.1111/j.1476-5381.1986.tb09497.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Amphetamine - metabolism Amphetamine - pharmacology Animals Benzyl Compounds - metabolism Biological and medical sciences Corpus Striatum - metabolism Half-Life Hydroxylation Hypothalamus - metabolism Male Medical sciences Neuropharmacology Octopamine - analogs & derivatives Pharmacology. Drug treatments Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Rats Stereoisomerism Tyramine - analogs & derivatives Tyramine - metabolism Tyramine - pharmacology |
| title | Stereoselective accumulation of hydroxylated metabolites of amphetamine in rat striatum and hypothalamus |
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