Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility
Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2009-09, Vol.239 (3), p.233-240 |
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| creator | Nojimoto, Fernanda D. Piffer, Renata C. Kiguti, Luiz Ricardo de A. Lameu, Claudiana de Camargo, Antônio C.M. Pereira, Oduvaldo C.M. Pupo, André S. |
| description | Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg
−
1
, ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca
2+ transients. Sibutramine 5 and 20 mg kg
−
1
reduced ejaculation latency whereas 50 mg kg
−
1
increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl
2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca
2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca
2+ may be involved in the delayed ejaculation observed with high doses of sibutramine. |
| doi_str_mv | 10.1016/j.taap.2009.05.021 |
| format | Article |
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−
1
, ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca
2+ transients. Sibutramine 5 and 20 mg kg
−
1
reduced ejaculation latency whereas 50 mg kg
−
1
increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl
2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca
2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca
2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2009.05.021</identifier><identifier>PMID: 19482040</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Abnormal ejaculation ; Adrenergic alpha-1 Receptor Agonists ; ADULTS ; Animals ; Appetite Depressants - adverse effects ; Biological and medical sciences ; Calcium - metabolism ; Calcium Chloride - pharmacology ; CALCIUM CHLORIDES ; CALCIUM IONS ; Carbachol - pharmacology ; Cell Line ; CENTRAL NERVOUS SYSTEM ; Cyclobutanes - adverse effects ; Dose-Response Relationship, Drug ; DOSES ; Ejaculation - drug effects ; Female ; Humans ; In Vitro Techniques ; Isometric Contraction - drug effects ; Male ; MALE GENITALS ; Medical sciences ; MEN ; METABOLIC DISEASES ; Neurotransmitter Agents - pharmacology ; NORADRENALINE ; Norepinephrine - pharmacology ; Premature ejaculation ; RATS ; Rats, Wistar ; Receptors, Muscarinic - metabolism ; Seminal vesicle ; Seminal Vesicles - drug effects ; Seminal Vesicles - metabolism ; SENSITIVITY ; Sibutramine ; Toxicology ; Vas deferens ; Vas Deferens - drug effects ; Vas Deferens - metabolism</subject><ispartof>Toxicology and applied pharmacology, 2009-09, Vol.239 (3), p.233-240</ispartof><rights>2009 Elsevier Inc.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-393faf94b4b77b8f81754ae36a33693e42bf0466dcdac0a13080b36a43a2973e3</citedby><cites>FETCH-LOGICAL-c487t-393faf94b4b77b8f81754ae36a33693e42bf0466dcdac0a13080b36a43a2973e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041008X09002208$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21949505$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19482040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21272648$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Nojimoto, Fernanda D.</creatorcontrib><creatorcontrib>Piffer, Renata C.</creatorcontrib><creatorcontrib>Kiguti, Luiz Ricardo de A.</creatorcontrib><creatorcontrib>Lameu, Claudiana</creatorcontrib><creatorcontrib>de Camargo, Antônio C.M.</creatorcontrib><creatorcontrib>Pereira, Oduvaldo C.M.</creatorcontrib><creatorcontrib>Pupo, André S.</creatorcontrib><title>Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg
−
1
, ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca
2+ transients. Sibutramine 5 and 20 mg kg
−
1
reduced ejaculation latency whereas 50 mg kg
−
1
increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl
2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca
2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca
2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Abnormal ejaculation</subject><subject>Adrenergic alpha-1 Receptor Agonists</subject><subject>ADULTS</subject><subject>Animals</subject><subject>Appetite Depressants - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Chloride - pharmacology</subject><subject>CALCIUM CHLORIDES</subject><subject>CALCIUM IONS</subject><subject>Carbachol - pharmacology</subject><subject>Cell Line</subject><subject>CENTRAL NERVOUS SYSTEM</subject><subject>Cyclobutanes - adverse effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>DOSES</subject><subject>Ejaculation - drug effects</subject><subject>Female</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Isometric Contraction - drug effects</subject><subject>Male</subject><subject>MALE GENITALS</subject><subject>Medical sciences</subject><subject>MEN</subject><subject>METABOLIC DISEASES</subject><subject>Neurotransmitter Agents - pharmacology</subject><subject>NORADRENALINE</subject><subject>Norepinephrine - pharmacology</subject><subject>Premature ejaculation</subject><subject>RATS</subject><subject>Rats, Wistar</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>Seminal vesicle</subject><subject>Seminal Vesicles - drug effects</subject><subject>Seminal Vesicles - metabolism</subject><subject>SENSITIVITY</subject><subject>Sibutramine</subject><subject>Toxicology</subject><subject>Vas deferens</subject><subject>Vas Deferens - drug effects</subject><subject>Vas Deferens - metabolism</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7uzqH_AgDaK3bisf_RHwIouuwooXBW-hOl3BDJnuMUkP7L837Qx685RQ9dRLvfUy9oJDw4F3b_dNRjw2AkA30DYg-CO246C7GqSUj9kOQPEaYPhxxa5T2kMBleJP2RXXahCgYMemL2vI_hioIufI5lQtrkp-XHPEg5-pWuaK9mjXgNmXP87TVjphqiZyFGlOf2qJCo2hOlHytqjZZS4KNvvg88Mz9sRhSPT88t6w7x8_fLv9VN9_vft8-_6-tmrocy21dOi0GtXY9-PgBt63Ckl2KGWnJSkxOlBdN9kJLSCXMMBYukqi0L0kecNenXWXlL1J1meyP8smczFmBBe96NRQqDdn6hiXXyulbA4-WQoBZ1rWZAT0mmu5geIM2rikFMmZY_QHjA-Gg9kSMHuzJWC2BAy0piRQhl5e1NfxQNO_kcvJC_D6AmCyGFzE2fr0lxMF1C20hXt35qhc7OQpboZotjT5uPmZFv-_PX4D3eKkpw</recordid><startdate>20090915</startdate><enddate>20090915</enddate><creator>Nojimoto, Fernanda D.</creator><creator>Piffer, Renata C.</creator><creator>Kiguti, Luiz Ricardo de A.</creator><creator>Lameu, Claudiana</creator><creator>de Camargo, Antônio C.M.</creator><creator>Pereira, Oduvaldo C.M.</creator><creator>Pupo, André S.</creator><general>Elsevier Inc</general><general>Elsevier</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>7QP</scope><scope>7ST</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>OTOTI</scope></search><sort><creationdate>20090915</creationdate><title>Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility</title><author>Nojimoto, Fernanda D. ; Piffer, Renata C. ; Kiguti, Luiz Ricardo de A. ; Lameu, Claudiana ; de Camargo, Antônio C.M. ; Pereira, Oduvaldo C.M. ; Pupo, André S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-393faf94b4b77b8f81754ae36a33693e42bf0466dcdac0a13080b36a43a2973e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Abnormal ejaculation</topic><topic>Adrenergic alpha-1 Receptor Agonists</topic><topic>ADULTS</topic><topic>Animals</topic><topic>Appetite Depressants - adverse effects</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Chloride - pharmacology</topic><topic>CALCIUM CHLORIDES</topic><topic>CALCIUM IONS</topic><topic>Carbachol - pharmacology</topic><topic>Cell Line</topic><topic>CENTRAL NERVOUS SYSTEM</topic><topic>Cyclobutanes - adverse effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>DOSES</topic><topic>Ejaculation - drug effects</topic><topic>Female</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Isometric Contraction - drug effects</topic><topic>Male</topic><topic>MALE GENITALS</topic><topic>Medical sciences</topic><topic>MEN</topic><topic>METABOLIC DISEASES</topic><topic>Neurotransmitter Agents - pharmacology</topic><topic>NORADRENALINE</topic><topic>Norepinephrine - pharmacology</topic><topic>Premature ejaculation</topic><topic>RATS</topic><topic>Rats, Wistar</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>Seminal vesicle</topic><topic>Seminal Vesicles - drug effects</topic><topic>Seminal Vesicles - metabolism</topic><topic>SENSITIVITY</topic><topic>Sibutramine</topic><topic>Toxicology</topic><topic>Vas deferens</topic><topic>Vas Deferens - drug effects</topic><topic>Vas Deferens - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nojimoto, Fernanda D.</creatorcontrib><creatorcontrib>Piffer, Renata C.</creatorcontrib><creatorcontrib>Kiguti, Luiz Ricardo de A.</creatorcontrib><creatorcontrib>Lameu, Claudiana</creatorcontrib><creatorcontrib>de Camargo, Antônio C.M.</creatorcontrib><creatorcontrib>Pereira, Oduvaldo C.M.</creatorcontrib><creatorcontrib>Pupo, André S.</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>Calcium & Calcified Tissue Abstracts</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nojimoto, Fernanda D.</au><au>Piffer, Renata C.</au><au>Kiguti, Luiz Ricardo de A.</au><au>Lameu, Claudiana</au><au>de Camargo, Antônio C.M.</au><au>Pereira, Oduvaldo C.M.</au><au>Pupo, André S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2009-09-15</date><risdate>2009</risdate><volume>239</volume><issue>3</issue><spage>233</spage><epage>240</epage><pages>233-240</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg
−
1
, ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca
2+ transients. Sibutramine 5 and 20 mg kg
−
1
reduced ejaculation latency whereas 50 mg kg
−
1
increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl
2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca
2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca
2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19482040</pmid><doi>10.1016/j.taap.2009.05.021</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Toxicology and applied pharmacology, 2009-09, Vol.239 (3), p.233-240 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_osti_scitechconnect_21272648 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 60 APPLIED LIFE SCIENCES Abnormal ejaculation Adrenergic alpha-1 Receptor Agonists ADULTS Animals Appetite Depressants - adverse effects Biological and medical sciences Calcium - metabolism Calcium Chloride - pharmacology CALCIUM CHLORIDES CALCIUM IONS Carbachol - pharmacology Cell Line CENTRAL NERVOUS SYSTEM Cyclobutanes - adverse effects Dose-Response Relationship, Drug DOSES Ejaculation - drug effects Female Humans In Vitro Techniques Isometric Contraction - drug effects Male MALE GENITALS Medical sciences MEN METABOLIC DISEASES Neurotransmitter Agents - pharmacology NORADRENALINE Norepinephrine - pharmacology Premature ejaculation RATS Rats, Wistar Receptors, Muscarinic - metabolism Seminal vesicle Seminal Vesicles - drug effects Seminal Vesicles - metabolism SENSITIVITY Sibutramine Toxicology Vas deferens Vas Deferens - drug effects Vas Deferens - metabolism |
| title | Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility |
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