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
Hauptverfasser: Goletiani, Nathalie V., Mendelson, Jack H., Sholar, Michelle B., Siegel, Arthur J., Skupny, Alicja, Mello, Nancy K.
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container_end_page 677
container_issue 4
container_start_page 667
container_title Pharmacology, biochemistry and behavior
container_volume 86
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
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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. 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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. 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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. 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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 &amp; dosage</topic><topic>Nalbuphine - adverse effects</topic><topic>Nalbuphine - blood</topic><topic>Nalbuphine - pharmacology</topic><topic>Narcotic Antagonists - administration &amp; 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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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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