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Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers.

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.
AuthorsNathalie V Goletiani, Jack H Mendelson, Michelle B Sholar, Arthur J Siegel, Alicja Skupny, Nancy K Mello
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 86 Issue 4 Pg. 667-77 (Apr 2007) ISSN: 0091-3057 [Print] United States
PMID17391744 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Adrenal Cortex Hormones
  • Narcotic Antagonists
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Adrenocorticotropic Hormone
  • Prolactin
  • Nalbuphine
  • Hydrocortisone
Topics
  • Adrenal Cortex Hormones (blood)
  • Adrenocorticotropic Hormone (blood)
  • Adult
  • Cocaine-Related Disorders (drug therapy, physiopathology)
  • Humans
  • Hydrocortisone (blood)
  • Hypothalamo-Hypophyseal System (drug effects, physiopathology)
  • Male
  • Nalbuphine (administration & dosage, adverse effects, blood, pharmacology)
  • Narcotic Antagonists (administration & dosage, adverse effects, blood, pharmacology)
  • Pituitary Gland, Anterior (drug effects, physiopathology)
  • Pituitary-Adrenal System (drug effects, physiopathology)
  • Prolactin (blood)
  • Receptors, Opioid, kappa (drug effects, physiology)
  • Receptors, Opioid, mu (drug effects, physiology)

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