1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover
A series of alkoxy-1,2,5-thiadiazole derivatives of arecoline was synthesized in an effort to develop M1 muscarinic agonists. The 3-butenyloxy, 2-butynyloxy, cyclopropylmethyloxy, and hexyloxy derivatives stimulated phosphoinositide turnover through muscarinic receptors in the rat hippocampus. The d...
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| Veröffentlicht in: | Brain research 1995-09, Vol.693 (1-2), p.118-123 |
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| creator | SUMUDRA PERIYASAMY MESSER, W. S ROKNICH, S SAUERBERG, P HOSS, W |
| description | A series of alkoxy-1,2,5-thiadiazole derivatives of arecoline was synthesized in an effort to develop M1 muscarinic agonists. The 3-butenyloxy, 2-butynyloxy, cyclopropylmethyloxy, and hexyloxy derivatives stimulated phosphoinositide turnover through muscarinic receptors in the rat hippocampus. The dose-response curves of 2-butynyloxy, cyclopropylmethyloxy and hexyloxy compound together was the same as the response of each separately. Pirenzepine was somewhat more potent than AF-DX 116 for inhibiting the responses produced by low concentrations of thiadiazole derivatives. The data suggest that the cyclopropylmethyloxy-TZTP derivative is functionally a selective M1 agonist. Molecular mechanics calculations indicate that the anti form of the 1,2,5-thiadiazole derivatives of arecoline may be active at M1 receptors. |
| doi_str_mv | 10.1016/0006-8993(95)00724-5 |
| format | Article |
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Molecular mechanics calculations indicate that the anti form of the 1,2,5-thiadiazole derivatives of arecoline may be active at M1 receptors.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/0006-8993(95)00724-5</identifier><identifier>PMID: 8653399</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier</publisher><subject>Animals ; Arecoline - analogs & derivatives ; Arecoline - chemistry ; Biochemistry and metabolism ; Biological and medical sciences ; Central nervous system ; Dose-Response Relationship, Drug ; Fundamental and applied biological sciences. 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S</creatorcontrib><creatorcontrib>ROKNICH, S</creatorcontrib><creatorcontrib>SAUERBERG, P</creatorcontrib><creatorcontrib>HOSS, W</creatorcontrib><title>1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>A series of alkoxy-1,2,5-thiadiazole derivatives of arecoline was synthesized in an effort to develop M1 muscarinic agonists. The 3-butenyloxy, 2-butynyloxy, cyclopropylmethyloxy, and hexyloxy derivatives stimulated phosphoinositide turnover through muscarinic receptors in the rat hippocampus. The dose-response curves of 2-butynyloxy, cyclopropylmethyloxy and hexyloxy compound together was the same as the response of each separately. Pirenzepine was somewhat more potent than AF-DX 116 for inhibiting the responses produced by low concentrations of thiadiazole derivatives. The data suggest that the cyclopropylmethyloxy-TZTP derivative is functionally a selective M1 agonist. Molecular mechanics calculations indicate that the anti form of the 1,2,5-thiadiazole derivatives of arecoline may be active at M1 receptors.</description><subject>Animals</subject><subject>Arecoline - analogs & derivatives</subject><subject>Arecoline - chemistry</subject><subject>Biochemistry and metabolism</subject><subject>Biological and medical sciences</subject><subject>Central nervous system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hippocampus - drug effects</subject><subject>Male</subject><subject>Muscarinic Agonists - pharmacology</subject><subject>Muscarinic Antagonists - pharmacology</subject><subject>Parasympatholytics - pharmacology</subject><subject>Phosphatidylinositols - metabolism</subject><subject>Pirenzepine - analogs & derivatives</subject><subject>Pirenzepine - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors, Muscarinic - drug effects</subject><subject>Thiadiazoles - chemistry</subject><subject>Thiadiazoles - pharmacology</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1LHDEUhoMoulr_QQu5kGLBqfmYZJLLIrYVFG_0OmSSM5gyOxmTzIL-erN12YuQnJznPRwehL5S8pMSKq8JIbJRWvNLLX4Q0rG2EQdoRVXHGslacohWe-QEneb8r5aca3KMjpUU9aVXaKBX7Eo0Ty_B-mDf4wjYQwobW8IGMo4DtglcHMMEOJewXkZbAD9QXH9hLjFl7OIyj-BxiXh-ibmeMMUcSvCAy5KmuIH0BR0NdsxwvrvP0PPv26ebv83945-7m1_3jWOtLI2yg4e2V9qpQVjPrfCMUqXq3tZLzrSXveMOKCGDA--dh763Djgnmnmh-Bn6_jl3TvF1gVzMOmQH42gniEs2XdcJThirYPsJuhRzTjCYOYW1TW-GErPVa7buzNad0cL812tEjX3bzV_6Nfh9aOez9i92fZudHYdkJxfyHuNSKlrJDyNRhLc</recordid><startdate>19950925</startdate><enddate>19950925</enddate><creator>SUMUDRA PERIYASAMY</creator><creator>MESSER, W. 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S ; ROKNICH, S ; SAUERBERG, P ; HOSS, W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c246t-8afde4b89c8f5ad3a5d21188003ad6329d6bc3ce100fceddcdebbace33092d583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Arecoline - analogs & derivatives</topic><topic>Arecoline - chemistry</topic><topic>Biochemistry and metabolism</topic><topic>Biological and medical sciences</topic><topic>Central nervous system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hippocampus - drug effects</topic><topic>Male</topic><topic>Muscarinic Agonists - pharmacology</topic><topic>Muscarinic Antagonists - pharmacology</topic><topic>Parasympatholytics - pharmacology</topic><topic>Phosphatidylinositols - metabolism</topic><topic>Pirenzepine - analogs & derivatives</topic><topic>Pirenzepine - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors, Muscarinic - drug effects</topic><topic>Thiadiazoles - chemistry</topic><topic>Thiadiazoles - pharmacology</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SUMUDRA PERIYASAMY</creatorcontrib><creatorcontrib>MESSER, W. S</creatorcontrib><creatorcontrib>ROKNICH, S</creatorcontrib><creatorcontrib>SAUERBERG, P</creatorcontrib><creatorcontrib>HOSS, W</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>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SUMUDRA PERIYASAMY</au><au>MESSER, W. S</au><au>ROKNICH, S</au><au>SAUERBERG, P</au><au>HOSS, W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>1995-09-25</date><risdate>1995</risdate><volume>693</volume><issue>1-2</issue><spage>118</spage><epage>123</epage><pages>118-123</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>A series of alkoxy-1,2,5-thiadiazole derivatives of arecoline was synthesized in an effort to develop M1 muscarinic agonists. The 3-butenyloxy, 2-butynyloxy, cyclopropylmethyloxy, and hexyloxy derivatives stimulated phosphoinositide turnover through muscarinic receptors in the rat hippocampus. The dose-response curves of 2-butynyloxy, cyclopropylmethyloxy and hexyloxy compound together was the same as the response of each separately. Pirenzepine was somewhat more potent than AF-DX 116 for inhibiting the responses produced by low concentrations of thiadiazole derivatives. The data suggest that the cyclopropylmethyloxy-TZTP derivative is functionally a selective M1 agonist. Molecular mechanics calculations indicate that the anti form of the 1,2,5-thiadiazole derivatives of arecoline may be active at M1 receptors.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier</pub><pmid>8653399</pmid><doi>10.1016/0006-8993(95)00724-5</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Arecoline - analogs & derivatives Arecoline - chemistry Biochemistry and metabolism Biological and medical sciences Central nervous system Dose-Response Relationship, Drug Fundamental and applied biological sciences. Psychology Hippocampus - drug effects Male Muscarinic Agonists - pharmacology Muscarinic Antagonists - pharmacology Parasympatholytics - pharmacology Phosphatidylinositols - metabolism Pirenzepine - analogs & derivatives Pirenzepine - pharmacology Rats Rats, Inbred Strains Receptors, Muscarinic - drug effects Thiadiazoles - chemistry Thiadiazoles - pharmacology Vertebrates: nervous system and sense organs |
| title | 1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover |
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