Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers
Nalbuphine (Nubain®) is a mixed action mu–kappa agonist used clinically for the management of pain. Nalbuphine and other mu–kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic–pituitary–adrenal (HPA) axis, but the effects of nalbuphine on t...
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Veröffentlicht in: | Pharmacology, biochemistry and behavior biochemistry and behavior, 2007-04, Vol.86 (4), p.667-677 |
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creator | Goletiani, Nathalie V. Mendelson, Jack H. Sholar, Michelle B. Siegel, Arthur J. Skupny, Alicja Mello, Nancy K. |
description | Nalbuphine (Nubain®) is a mixed action mu–kappa agonist used clinically for the management of pain. Nalbuphine and other mu–kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic–pituitary–adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (
P
=
.04) and reached peak levels of 22.1
±
7.1 ng/ml and 54.1
±
11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of “Sick,” “Bad” and “Dizzy” were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (
P
=
.05–.0001), and were significantly correlated with increases in PRL (
P
=
.05–.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol. |
doi_str_mv | 10.1016/j.pbb.2007.02.012 |
format | Article |
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P
=
.04) and reached peak levels of 22.1
±
7.1 ng/ml and 54.1
±
11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of “Sick,” “Bad” and “Dizzy” were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (
P
=
.05–.0001), and were significantly correlated with increases in PRL (
P
=
.05–.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.</description><identifier>ISSN: 0091-3057</identifier><identifier>EISSN: 1873-5177</identifier><identifier>DOI: 10.1016/j.pbb.2007.02.012</identifier><identifier>PMID: 17391744</identifier><identifier>CODEN: PBBHAU</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adrenal Cortex Hormones - blood ; Adrenocorticotropic Hormone - blood ; Adult ; Biological and medical sciences ; Cocaine ; Cocaine-Related Disorders - drug therapy ; Cocaine-Related Disorders - physiopathology ; Human ; Humans ; Hydrocortisone - blood ; Hypothalamo-Hypophyseal System - drug effects ; Hypothalamo-Hypophyseal System - physiopathology ; Male ; Medical sciences ; Nalbuphine ; Nalbuphine - administration & dosage ; Nalbuphine - adverse effects ; Nalbuphine - blood ; Nalbuphine - pharmacology ; Narcotic Antagonists - administration & dosage ; Narcotic Antagonists - adverse effects ; Narcotic Antagonists - blood ; Narcotic Antagonists - pharmacology ; Neuropharmacology ; Opioids ; Pharmacology. Drug treatments ; Pituitary Gland, Anterior - drug effects ; Pituitary Gland, Anterior - physiopathology ; Pituitary-Adrenal System - drug effects ; Pituitary-Adrenal System - physiopathology ; Prolactin ; Prolactin - blood ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Receptors, Opioid, kappa - drug effects ; Receptors, Opioid, kappa - physiology ; Receptors, Opioid, mu - drug effects ; Receptors, Opioid, mu - physiology</subject><ispartof>Pharmacology, biochemistry and behavior, 2007-04, Vol.86 (4), p.667-677</ispartof><rights>2007 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-4f32733d5508037e118918ee592b30ae8cdc804fefcfefdf079d21e8ee6cdaad3</citedby><cites>FETCH-LOGICAL-c510t-4f32733d5508037e118918ee592b30ae8cdc804fefcfefdf079d21e8ee6cdaad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0091305707000834$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18826258$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17391744$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goletiani, Nathalie V.</creatorcontrib><creatorcontrib>Mendelson, Jack H.</creatorcontrib><creatorcontrib>Sholar, Michelle B.</creatorcontrib><creatorcontrib>Siegel, Arthur J.</creatorcontrib><creatorcontrib>Skupny, Alicja</creatorcontrib><creatorcontrib>Mello, Nancy K.</creatorcontrib><title>Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers</title><title>Pharmacology, biochemistry and behavior</title><addtitle>Pharmacol Biochem Behav</addtitle><description>Nalbuphine (Nubain®) is a mixed action mu–kappa agonist used clinically for the management of pain. Nalbuphine and other mu–kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic–pituitary–adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (
P
=
.04) and reached peak levels of 22.1
±
7.1 ng/ml and 54.1
±
11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of “Sick,” “Bad” and “Dizzy” were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (
P
=
.05–.0001), and were significantly correlated with increases in PRL (
P
=
.05–.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.</description><subject>Adrenal Cortex Hormones - blood</subject><subject>Adrenocorticotropic Hormone - blood</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Cocaine</subject><subject>Cocaine-Related Disorders - drug therapy</subject><subject>Cocaine-Related Disorders - physiopathology</subject><subject>Human</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Hypothalamo-Hypophyseal System - drug effects</subject><subject>Hypothalamo-Hypophyseal System - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nalbuphine</subject><subject>Nalbuphine - administration & dosage</subject><subject>Nalbuphine - adverse effects</subject><subject>Nalbuphine - blood</subject><subject>Nalbuphine - pharmacology</subject><subject>Narcotic Antagonists - administration & dosage</subject><subject>Narcotic Antagonists - adverse effects</subject><subject>Narcotic Antagonists - blood</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Neuropharmacology</subject><subject>Opioids</subject><subject>Pharmacology. Drug treatments</subject><subject>Pituitary Gland, Anterior - drug effects</subject><subject>Pituitary Gland, Anterior - physiopathology</subject><subject>Pituitary-Adrenal System - drug effects</subject><subject>Pituitary-Adrenal System - physiopathology</subject><subject>Prolactin</subject><subject>Prolactin - blood</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Receptors, Opioid, kappa - drug effects</subject><subject>Receptors, Opioid, kappa - physiology</subject><subject>Receptors, Opioid, mu - drug effects</subject><subject>Receptors, Opioid, mu - physiology</subject><issn>0091-3057</issn><issn>1873-5177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7rj6A7xILnrrtpJ0TzIIgizrByx40XNIJxUnQ3fSm3QP-O_NOIOrFw9FQdVTb1XyEvKSQcuAbd8e2nkYWg4gW-AtMP6IbJiSoumZlI_JBmDHGgG9vCLPSjkAQMe38im5YlLsmOy6Dbm_9R7tUmjyNJpxWOd9iEhTpCYumEPKdA7LGhaTf9aSo8ZlrCDdpzyliOV3sazDoaqEI9KMZU6x1EaIdDIjUpusOWmaYS2Yy3PyxJux4ItLvibfP95-u_nc3H399OXmw11jewZL03nBpRCu70GBkMiY2jGF2O_4IMCgss4q6Dx6W8N5kDvHGVZia50xTlyT92fdeR0mdBbjks2o5xym-hadTND_dmLY6x_pqDlwUKKrAm8uAjndr1gWPYVicRxNxLSWym1533WiguwM2pxKyej_LGGgT0bpg65G6ZNRGriuRtWZV39f9zBxcaYCry-AKdaMPptoQ3nglOJ1varcuzOH9S-PAbMuNmC06EKulmiXwn_O-AXAkbSr</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Goletiani, Nathalie V.</creator><creator>Mendelson, Jack H.</creator><creator>Sholar, Michelle B.</creator><creator>Siegel, Arthur J.</creator><creator>Skupny, Alicja</creator><creator>Mello, Nancy K.</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7QG</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20070401</creationdate><title>Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers</title><author>Goletiani, Nathalie V. ; Mendelson, Jack H. ; Sholar, Michelle B. ; Siegel, Arthur J. ; Skupny, Alicja ; Mello, Nancy K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-4f32733d5508037e118918ee592b30ae8cdc804fefcfefdf079d21e8ee6cdaad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adrenal Cortex Hormones - blood</topic><topic>Adrenocorticotropic Hormone - blood</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Cocaine</topic><topic>Cocaine-Related Disorders - drug therapy</topic><topic>Cocaine-Related Disorders - physiopathology</topic><topic>Human</topic><topic>Humans</topic><topic>Hydrocortisone - blood</topic><topic>Hypothalamo-Hypophyseal System - drug effects</topic><topic>Hypothalamo-Hypophyseal System - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nalbuphine</topic><topic>Nalbuphine - administration & dosage</topic><topic>Nalbuphine - adverse effects</topic><topic>Nalbuphine - blood</topic><topic>Nalbuphine - pharmacology</topic><topic>Narcotic Antagonists - administration & dosage</topic><topic>Narcotic Antagonists - adverse effects</topic><topic>Narcotic Antagonists - blood</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Neuropharmacology</topic><topic>Opioids</topic><topic>Pharmacology. Drug treatments</topic><topic>Pituitary Gland, Anterior - drug effects</topic><topic>Pituitary Gland, Anterior - physiopathology</topic><topic>Pituitary-Adrenal System - drug effects</topic><topic>Pituitary-Adrenal System - physiopathology</topic><topic>Prolactin</topic><topic>Prolactin - blood</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Receptors, Opioid, kappa - drug effects</topic><topic>Receptors, Opioid, kappa - physiology</topic><topic>Receptors, Opioid, mu - drug effects</topic><topic>Receptors, Opioid, mu - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goletiani, Nathalie V.</creatorcontrib><creatorcontrib>Mendelson, Jack H.</creatorcontrib><creatorcontrib>Sholar, Michelle B.</creatorcontrib><creatorcontrib>Siegel, Arthur J.</creatorcontrib><creatorcontrib>Skupny, Alicja</creatorcontrib><creatorcontrib>Mello, Nancy K.</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>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pharmacology, biochemistry and behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goletiani, Nathalie V.</au><au>Mendelson, Jack H.</au><au>Sholar, Michelle B.</au><au>Siegel, Arthur J.</au><au>Skupny, Alicja</au><au>Mello, Nancy K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers</atitle><jtitle>Pharmacology, biochemistry and behavior</jtitle><addtitle>Pharmacol Biochem Behav</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>86</volume><issue>4</issue><spage>667</spage><epage>677</epage><pages>667-677</pages><issn>0091-3057</issn><eissn>1873-5177</eissn><coden>PBBHAU</coden><abstract>Nalbuphine (Nubain®) is a mixed action mu–kappa agonist used clinically for the management of pain. Nalbuphine and other mu–kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic–pituitary–adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (
P
=
.04) and reached peak levels of 22.1
±
7.1 ng/ml and 54.1
±
11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of “Sick,” “Bad” and “Dizzy” were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (
P
=
.05–.0001), and were significantly correlated with increases in PRL (
P
=
.05–.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17391744</pmid><doi>10.1016/j.pbb.2007.02.012</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | Adrenal Cortex Hormones - blood Adrenocorticotropic Hormone - blood Adult Biological and medical sciences Cocaine Cocaine-Related Disorders - drug therapy Cocaine-Related Disorders - physiopathology Human Humans Hydrocortisone - blood Hypothalamo-Hypophyseal System - drug effects Hypothalamo-Hypophyseal System - physiopathology Male Medical sciences Nalbuphine Nalbuphine - administration & dosage Nalbuphine - adverse effects Nalbuphine - blood Nalbuphine - pharmacology Narcotic Antagonists - administration & dosage Narcotic Antagonists - adverse effects Narcotic Antagonists - blood Narcotic Antagonists - pharmacology Neuropharmacology Opioids Pharmacology. Drug treatments Pituitary Gland, Anterior - drug effects Pituitary Gland, Anterior - physiopathology Pituitary-Adrenal System - drug effects Pituitary-Adrenal System - physiopathology Prolactin Prolactin - blood Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Receptors, Opioid, kappa - drug effects Receptors, Opioid, kappa - physiology Receptors, Opioid, mu - drug effects Receptors, Opioid, mu - physiology |
title | Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers |
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