Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity
We previously reported that the κ agonists with mixed μ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ ago...
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| Veröffentlicht in: | European journal of pharmacology 2014-10, Vol.740, p.455-463 |
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| creator | Sun, Jian-Feng Wang, Yu-Hua Chai, Jing-Rui Li, Fu-Ying Hang, Ai Lu, Gang Tao, Yi-Min Cheng, Yun Chi, Zhi-Qiang Neumeyer, John L. Zhang, Ao Liu, Jing-Gen Wang, Yu-Jun |
| description | We previously reported that the κ agonists with mixed μ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and μ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and μ agonist/antagonist may have utility for the treatment of drug dependence. |
| doi_str_mv | 10.1016/j.ejphar.2014.06.045 |
| format | Article |
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The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and μ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and μ agonist/antagonist may have utility for the treatment of drug dependence.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2014.06.045</identifier><identifier>PMID: 24998879</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Analgesics, Opioid - administration & dosage ; Animals ; Antinociception ; Conditioning (Psychology) ; CPP ; Drug-Seeking Behavior - drug effects ; Heroin Dependence - drug therapy ; Heroin self-administration ; Male ; Mice ; Morphinans - therapeutic use ; Morphine - administration & dosage ; Narcotic Antagonists - therapeutic use ; Pain - drug therapy ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa - agonists ; Receptors, Opioid, mu - agonists ; Receptors, Opioid, mu - antagonists & inhibitors ; Reinstatement of drug-seeking behavior ; Sedation ; Self Administration ; κ agonist and μ agonist/antagonist</subject><ispartof>European journal of pharmacology, 2014-10, Vol.740, p.455-463</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-25cc21708de5bd5357a8478689f166f38df11cb673cc98e02140dd13e14b298c3</citedby><cites>FETCH-LOGICAL-c432t-25cc21708de5bd5357a8478689f166f38df11cb673cc98e02140dd13e14b298c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2014.06.045$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24998879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Jian-Feng</creatorcontrib><creatorcontrib>Wang, Yu-Hua</creatorcontrib><creatorcontrib>Chai, Jing-Rui</creatorcontrib><creatorcontrib>Li, Fu-Ying</creatorcontrib><creatorcontrib>Hang, Ai</creatorcontrib><creatorcontrib>Lu, Gang</creatorcontrib><creatorcontrib>Tao, Yi-Min</creatorcontrib><creatorcontrib>Cheng, Yun</creatorcontrib><creatorcontrib>Chi, Zhi-Qiang</creatorcontrib><creatorcontrib>Neumeyer, John L.</creatorcontrib><creatorcontrib>Zhang, Ao</creatorcontrib><creatorcontrib>Liu, Jing-Gen</creatorcontrib><creatorcontrib>Wang, Yu-Jun</creatorcontrib><title>Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>We previously reported that the κ agonists with mixed μ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and μ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and μ agonist/antagonist may have utility for the treatment of drug dependence.</description><subject>Analgesics, Opioid - administration & dosage</subject><subject>Animals</subject><subject>Antinociception</subject><subject>Conditioning (Psychology)</subject><subject>CPP</subject><subject>Drug-Seeking Behavior - drug effects</subject><subject>Heroin Dependence - drug therapy</subject><subject>Heroin self-administration</subject><subject>Male</subject><subject>Mice</subject><subject>Morphinans - therapeutic use</subject><subject>Morphine - administration & dosage</subject><subject>Narcotic Antagonists - therapeutic use</subject><subject>Pain - drug therapy</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Opioid, kappa - agonists</subject><subject>Receptors, Opioid, mu - agonists</subject><subject>Receptors, Opioid, mu - antagonists & inhibitors</subject><subject>Reinstatement of drug-seeking behavior</subject><subject>Sedation</subject><subject>Self Administration</subject><subject>κ agonist and μ agonist/antagonist</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhiMEokPhDRDykgWZ2s7VG6SqKhepQBfD2nKck-aMkjjYJ62mj4Z4A6Q-E55O2yUr6_j__nPRnyRvBV8LLsqT7Rq2c2_8WnKRr3m55nnxLFmJulIpr4R8nqx4VFKplDpKXoWw5ZwXShYvkyOZK1VHcJX8vYwtRmPd4K7QmoHZWBtL4PHWELqJmall1IM3MyyEls2OYCKMaOf8XmHkwdAYP5nrmJvRYctMswRgN0g9O91cfkvPNx9iJ_Y9Bep3AwtLEwhpIYjoiJOjHs1tXGJ0fu5xiui99-43M1duwkD3e9z9eSxPzERPiiW8Rtq9Tl50Zgjw5uE9Tn5-Ot-cfUkvfnz-enZ6kdo8k5TKwlopKl63UDRtkRWVqfOqLmvVibLssrrthLBNWWXWqhq4FDlvW5GByBupapsdJ-8PfWfvfi0QSI8YLAyDmcAtQYuiqAupqkxEND-g1rsQPHR69jgav9OC632MeqsPMep9jJqXOsYYbe8eJizNCO2T6TG3CHw8ABDvvEbwOliEyUKLHizp1uH_J_wDv8y3bA</recordid><startdate>20141005</startdate><enddate>20141005</enddate><creator>Sun, Jian-Feng</creator><creator>Wang, Yu-Hua</creator><creator>Chai, Jing-Rui</creator><creator>Li, Fu-Ying</creator><creator>Hang, Ai</creator><creator>Lu, Gang</creator><creator>Tao, Yi-Min</creator><creator>Cheng, Yun</creator><creator>Chi, Zhi-Qiang</creator><creator>Neumeyer, John L.</creator><creator>Zhang, Ao</creator><creator>Liu, Jing-Gen</creator><creator>Wang, Yu-Jun</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20141005</creationdate><title>Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity</title><author>Sun, Jian-Feng ; Wang, Yu-Hua ; Chai, Jing-Rui ; Li, Fu-Ying ; Hang, Ai ; Lu, Gang ; Tao, Yi-Min ; Cheng, Yun ; Chi, Zhi-Qiang ; Neumeyer, John L. ; Zhang, Ao ; Liu, Jing-Gen ; Wang, Yu-Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-25cc21708de5bd5357a8478689f166f38df11cb673cc98e02140dd13e14b298c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analgesics, Opioid - administration & dosage</topic><topic>Animals</topic><topic>Antinociception</topic><topic>Conditioning (Psychology)</topic><topic>CPP</topic><topic>Drug-Seeking Behavior - drug effects</topic><topic>Heroin Dependence - drug therapy</topic><topic>Heroin self-administration</topic><topic>Male</topic><topic>Mice</topic><topic>Morphinans - therapeutic use</topic><topic>Morphine - administration & dosage</topic><topic>Narcotic Antagonists - therapeutic use</topic><topic>Pain - drug therapy</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Opioid, kappa - agonists</topic><topic>Receptors, Opioid, mu - agonists</topic><topic>Receptors, Opioid, mu - antagonists & inhibitors</topic><topic>Reinstatement of drug-seeking behavior</topic><topic>Sedation</topic><topic>Self Administration</topic><topic>κ agonist and μ agonist/antagonist</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Jian-Feng</creatorcontrib><creatorcontrib>Wang, Yu-Hua</creatorcontrib><creatorcontrib>Chai, Jing-Rui</creatorcontrib><creatorcontrib>Li, Fu-Ying</creatorcontrib><creatorcontrib>Hang, Ai</creatorcontrib><creatorcontrib>Lu, Gang</creatorcontrib><creatorcontrib>Tao, Yi-Min</creatorcontrib><creatorcontrib>Cheng, Yun</creatorcontrib><creatorcontrib>Chi, Zhi-Qiang</creatorcontrib><creatorcontrib>Neumeyer, John L.</creatorcontrib><creatorcontrib>Zhang, Ao</creatorcontrib><creatorcontrib>Liu, Jing-Gen</creatorcontrib><creatorcontrib>Wang, Yu-Jun</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><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Jian-Feng</au><au>Wang, Yu-Hua</au><au>Chai, Jing-Rui</au><au>Li, Fu-Ying</au><au>Hang, Ai</au><au>Lu, Gang</au><au>Tao, Yi-Min</au><au>Cheng, Yun</au><au>Chi, Zhi-Qiang</au><au>Neumeyer, John L.</au><au>Zhang, Ao</au><au>Liu, Jing-Gen</au><au>Wang, Yu-Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2014-10-05</date><risdate>2014</risdate><volume>740</volume><spage>455</spage><epage>463</epage><pages>455-463</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>We previously reported that the κ agonists with mixed μ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and μ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and μ agonist/antagonist may have utility for the treatment of drug dependence.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24998879</pmid><doi>10.1016/j.ejphar.2014.06.045</doi><tpages>9</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2014-10, Vol.740, p.455-463 |
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| subjects | Analgesics, Opioid - administration & dosage Animals Antinociception Conditioning (Psychology) CPP Drug-Seeking Behavior - drug effects Heroin Dependence - drug therapy Heroin self-administration Male Mice Morphinans - therapeutic use Morphine - administration & dosage Narcotic Antagonists - therapeutic use Pain - drug therapy Rats, Sprague-Dawley Receptors, Opioid, kappa - agonists Receptors, Opioid, mu - agonists Receptors, Opioid, mu - antagonists & inhibitors Reinstatement of drug-seeking behavior Sedation Self Administration κ agonist and μ agonist/antagonist |
| title | Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity |
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