Selective and Potent Analgetics Derived from Cannabinoids
: Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabi...
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| Veröffentlicht in: | Journal of clinical pharmacology 1981-08, Vol.21 (S1), p.271S-282S |
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| container_end_page | 282S |
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| container_issue | S1 |
| container_start_page | 271S |
| container_title | Journal of clinical pharmacology |
| container_volume | 21 |
| creator | JOHNSON, M. R. MELVIN, L. S. ALTHUIS, T. H. BINDRA, J. S. HARBERT, C. A. MILNE, G. M. WEISSMAN, A. |
| description | : Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabinol (HHC). A new grouping, the 1‐methyl‐4‐phenylbutyloxy C‐3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity. |
| doi_str_mv | 10.1002/j.1552-4604.1981.tb02605.x |
| format | Article |
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Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. 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Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Cannabinoids - chemical synthesis</subject><subject>Cannabinoids - pharmacology</subject><subject>Dronabinol - pharmacology</subject><subject>Mice</subject><subject>Phenanthrenes - pharmacology</subject><subject>Phenanthridines - pharmacology</subject><subject>Phenols - pharmacology</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1981</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE1Pg0AQhjdGU2v1J5gQD97AWdhdWE82VFubpjZ-HjcLDIZKobJU238vhKZ3TzPJO_NM5iHkioJDAdybpUM5d20mgDlUBtSpI3AFcGd7RPqH6Jj0ASS1XR_glJwZswSggnHaIz3h-jTwvD6RL5hjXGc_aOkisRZljUVtDQudf2KdxcYaYdWEiZVW5coKdVHoKCvKLDHn5CTVucGLfR2Qt4f713Biz57Gj-FwZscMJLcjZFJwKmQkNcgAPRpITAR4oFkc-DzWUoALGnmCoGUqJLDAd2kUyRSC1PMG5Lrjrqvye4OmVqvMxJjnusByY5Tv-Yy5LGgGb7vBuCqNqTBV6ypb6WqnKKjWm1qqVo5q5ajWm9p7U9tm-XJ_ZROtMDms7kU1-V2X_2Y57v5BVtNwMWnbBmF3iMzUuD0gdPWlRPMEVx_zsXpn_tx_Hk3V1PsDtSKLXw</recordid><startdate>198108</startdate><enddate>198108</enddate><creator>JOHNSON, M. R.</creator><creator>MELVIN, L. S.</creator><creator>ALTHUIS, T. H.</creator><creator>BINDRA, J. S.</creator><creator>HARBERT, C. A.</creator><creator>MILNE, G. M.</creator><creator>WEISSMAN, A.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>198108</creationdate><title>Selective and Potent Analgetics Derived from Cannabinoids</title><author>JOHNSON, M. R. ; MELVIN, L. S. ; ALTHUIS, T. H. ; BINDRA, J. S. ; HARBERT, C. A. ; MILNE, G. M. ; WEISSMAN, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4095-be4965169b9a098e3189ed6030a4c875ca96020ae5de0a9f69048721bb9f08f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1981</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Cannabinoids - chemical synthesis</topic><topic>Cannabinoids - pharmacology</topic><topic>Dronabinol - pharmacology</topic><topic>Mice</topic><topic>Phenanthrenes - pharmacology</topic><topic>Phenanthridines - pharmacology</topic><topic>Phenols - pharmacology</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JOHNSON, M. R.</creatorcontrib><creatorcontrib>MELVIN, L. S.</creatorcontrib><creatorcontrib>ALTHUIS, T. H.</creatorcontrib><creatorcontrib>BINDRA, J. S.</creatorcontrib><creatorcontrib>HARBERT, C. A.</creatorcontrib><creatorcontrib>MILNE, G. M.</creatorcontrib><creatorcontrib>WEISSMAN, A.</creatorcontrib><collection>Istex</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 clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JOHNSON, M. R.</au><au>MELVIN, L. S.</au><au>ALTHUIS, T. H.</au><au>BINDRA, J. S.</au><au>HARBERT, C. A.</au><au>MILNE, G. M.</au><au>WEISSMAN, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective and Potent Analgetics Derived from Cannabinoids</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>1981-08</date><risdate>1981</risdate><volume>21</volume><issue>S1</issue><spage>271S</spage><epage>282S</epage><pages>271S-282S</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><abstract>: Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabinol (HHC). A new grouping, the 1‐methyl‐4‐phenylbutyloxy C‐3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>6271833</pmid><doi>10.1002/j.1552-4604.1981.tb02605.x</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-2700 |
| ispartof | Journal of clinical pharmacology, 1981-08, Vol.21 (S1), p.271S-282S |
| issn | 0091-2700 1552-4604 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Analgesics Animals Cannabinoids - chemical synthesis Cannabinoids - pharmacology Dronabinol - pharmacology Mice Phenanthrenes - pharmacology Phenanthridines - pharmacology Phenols - pharmacology Stereoisomerism Structure-Activity Relationship |
| title | Selective and Potent Analgetics Derived from Cannabinoids |
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