Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats
Methcathinone (MCAT; ), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although (-)MCAT is several-fold more potent than (+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug d...
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| Veröffentlicht in: | ACS chemical neuroscience 2020-06, Vol.11 (12), p.1762-1769 |
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| creator | Davies, Rachel A Baird, Tyson R Nguyen, Vy T Ruiz, Brian Sakloth, Farhana Eltit, Jose M Negus, S Stevens Glennon, Richard A |
| description | Methcathinone (MCAT;
), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although
(-)MCAT is several-fold more potent than
(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (
., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats,
(-)MCAT was approximately twice as potent as its
-enantiomer. Achiral analogs, α-methyl MCAT (
) and α-
methyl MCAT (
), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents. |
| doi_str_mv | 10.1021/acschemneuro.9b00617 |
| format | Article |
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), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although
(-)MCAT is several-fold more potent than
(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (
., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats,
(-)MCAT was approximately twice as potent as its
-enantiomer. Achiral analogs, α-methyl MCAT (
) and α-
methyl MCAT (
), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.</description><identifier>ISSN: 1948-7193</identifier><identifier>EISSN: 1948-7193</identifier><identifier>DOI: 10.1021/acschemneuro.9b00617</identifier><identifier>PMID: 32356961</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Dopamine Plasma Membrane Transport Proteins ; Norepinephrine Plasma Membrane Transport Proteins ; Propiophenones ; Rats ; Self Stimulation ; Serotonin Plasma Membrane Transport Proteins</subject><ispartof>ACS chemical neuroscience, 2020-06, Vol.11 (12), p.1762-1769</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-a94c4d2c766a902e77b0b4cd40c7e90514bc551cd745532b75a85629aa235f533</citedby><cites>FETCH-LOGICAL-c409t-a94c4d2c766a902e77b0b4cd40c7e90514bc551cd745532b75a85629aa235f533</cites><orcidid>0000-0002-3600-9045 ; 0000-0002-5288-1669</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,2752,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32356961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Davies, Rachel A</creatorcontrib><creatorcontrib>Baird, Tyson R</creatorcontrib><creatorcontrib>Nguyen, Vy T</creatorcontrib><creatorcontrib>Ruiz, Brian</creatorcontrib><creatorcontrib>Sakloth, Farhana</creatorcontrib><creatorcontrib>Eltit, Jose M</creatorcontrib><creatorcontrib>Negus, S Stevens</creatorcontrib><creatorcontrib>Glennon, Richard A</creatorcontrib><title>Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats</title><title>ACS chemical neuroscience</title><addtitle>ACS Chem Neurosci</addtitle><description>Methcathinone (MCAT;
), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although
(-)MCAT is several-fold more potent than
(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (
., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats,
(-)MCAT was approximately twice as potent as its
-enantiomer. Achiral analogs, α-methyl MCAT (
) and α-
methyl MCAT (
), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.</description><subject>Animals</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Norepinephrine Plasma Membrane Transport Proteins</subject><subject>Propiophenones</subject><subject>Rats</subject><subject>Self Stimulation</subject><subject>Serotonin Plasma Membrane Transport Proteins</subject><issn>1948-7193</issn><issn>1948-7193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctu1DAUtRAVfcAfIOQlC1LsJLbjFRpVUEZqVakzrK0bx5kYJfZgO634Gb4VRzNUw-pa9zx8dA9C7ym5pqSkn0FHPZjJmTn4a9kSwql4hS6orJtCUFm9Pnmfo8sYf2aKJA1_g86rsmJccnqB_qzdk4nJ7iBZ77DvcRoMftgnq2HE6-gnE-Kyvjdp0JAG67wznzC4Dm-fPV7pwYbMXDkY_S5mIOF77zxM1hm8DeDi3oe0mCwS6_DapQA6AzbLNmbsi02y0zweAmzS3FkTF-IjpPgWnfUwRvPuOK_Qj29ftzffi7uH2_XN6q7QNZGpAFnruiu14BwkKY0QLWlr3dVECyMJo3WrGaO6EzVjVdkKBg3jpQTIh-hZVV2hLwff_dxOptNmCTmqfbAThN_Kg1X_I84OauefFCWESiZldvh4dAj-15xPqiYbtRlHcMbPUZWVFLwhrOGZWh-oOvgYg-lf_qFELd2q027Vsdss-3Ca8UX0r8zqL715p6o</recordid><startdate>20200617</startdate><enddate>20200617</enddate><creator>Davies, Rachel A</creator><creator>Baird, Tyson R</creator><creator>Nguyen, Vy T</creator><creator>Ruiz, Brian</creator><creator>Sakloth, Farhana</creator><creator>Eltit, Jose M</creator><creator>Negus, S Stevens</creator><creator>Glennon, Richard A</creator><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3600-9045</orcidid><orcidid>https://orcid.org/0000-0002-5288-1669</orcidid></search><sort><creationdate>20200617</creationdate><title>Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats</title><author>Davies, Rachel A ; Baird, Tyson R ; Nguyen, Vy T ; Ruiz, Brian ; Sakloth, Farhana ; Eltit, Jose M ; Negus, S Stevens ; Glennon, Richard A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-a94c4d2c766a902e77b0b4cd40c7e90514bc551cd745532b75a85629aa235f533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>Norepinephrine Plasma Membrane Transport Proteins</topic><topic>Propiophenones</topic><topic>Rats</topic><topic>Self Stimulation</topic><topic>Serotonin Plasma Membrane Transport Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Davies, Rachel A</creatorcontrib><creatorcontrib>Baird, Tyson R</creatorcontrib><creatorcontrib>Nguyen, Vy T</creatorcontrib><creatorcontrib>Ruiz, Brian</creatorcontrib><creatorcontrib>Sakloth, Farhana</creatorcontrib><creatorcontrib>Eltit, Jose M</creatorcontrib><creatorcontrib>Negus, S Stevens</creatorcontrib><creatorcontrib>Glennon, Richard A</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>ACS chemical neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Davies, Rachel A</au><au>Baird, Tyson R</au><au>Nguyen, Vy T</au><au>Ruiz, Brian</au><au>Sakloth, Farhana</au><au>Eltit, Jose M</au><au>Negus, S Stevens</au><au>Glennon, Richard A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats</atitle><jtitle>ACS chemical neuroscience</jtitle><addtitle>ACS Chem Neurosci</addtitle><date>2020-06-17</date><risdate>2020</risdate><volume>11</volume><issue>12</issue><spage>1762</spage><epage>1769</epage><pages>1762-1769</pages><issn>1948-7193</issn><eissn>1948-7193</eissn><abstract>Methcathinone (MCAT;
), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although
(-)MCAT is several-fold more potent than
(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (
., as releasing agents) and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats,
(-)MCAT was approximately twice as potent as its
-enantiomer. Achiral analogs, α-methyl MCAT (
) and α-
methyl MCAT (
), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.</abstract><cop>United States</cop><pmid>32356961</pmid><doi>10.1021/acschemneuro.9b00617</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3600-9045</orcidid><orcidid>https://orcid.org/0000-0002-5288-1669</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | ACS chemical neuroscience, 2020-06, Vol.11 (12), p.1762-1769 |
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| source | MEDLINE; ACS Publications |
| subjects | Animals Dopamine Plasma Membrane Transport Proteins Norepinephrine Plasma Membrane Transport Proteins Propiophenones Rats Self Stimulation Serotonin Plasma Membrane Transport Proteins |
| title | Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats |
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