HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Delitala, G Articles by Grossman, A B Search for Related Content PubMed PubMed Citation Articles by Delitala, G Articles by Grossman, A B

Opioid peptides are well established as potent inhibitors of the pituitary-adrenal axis, while ₁-adrenoceptor drugs have recently been shown to stimulate this axis: both classes of agents appear to work principally above the level of the pituitary, most probable directly on the hypothalamus. There is also evidence that these drugs interact in their control of pituitary-adrenal function, although the specific hypothalamic releasing hormone involved has remained unclear. We have therefore carried out a study into the interaction of methoxamine, an ₁-adrenoceptor agonist and naloxone, an opioid antagonist, together with human corticotrophin-releasing hormone (CRH), in a group of healthy volunteers in order to establish the mode of action of these drugs.

The following drugs were administered to a group of seven healthy male subjects in a randomized double-blind manner: methoxamine (6 µg/kg per min over 3 h); naloxone (10 mg bolus); human CRH (100 pg bolus); methoxamine plus CRH; naloxone plus CRH; methoxamine plus naloxone; saline (control). Plasma ACTH and serum cortisol were measured at intervals in each subject, and blood pressure and pulse rate recorded with each sample.

Both CRH and naloxone produce a marked rise in ACTH and cortisol, peaking at approximately 45 min after infusion. In combination, the drugs produced a peak response in plasma ACTH at the same time, but its magnitude was greater than that after either drug alone. Methoxamine produced a rise in plasma ACTH which was maximal at approximately 75 min, as well as a peak rise in serum cortisol at 120 min. This was greater than after either CRH or naloxone alone but, in combination, both drugs produced peak responses not significantly greater than when methoxamine alone was given.

While the interaction of drugs with differing pharmacokinetic profiles renders interpretation difficult, our data suggest that naloxone increases pituitary-adrenal activity via a mechanism independent of CRH, most probably hypothalamic vasopressin. This, albeit indirect, evidence suggests that ₁-adrenoceptor activation with methoxamine activates hypothalamic pathways involving both endogenous CRH and vasopressin.

Journal of Endocrinology (1994) 141, 163–168

This article has been cited by other articles:

				M. al'Absi, L. E. Wittmers, D. Hatsukami, and R. Westra Blunted Opiate Modulation of Hypothalamic-Pituitary-Adrenocortical Activity in Men and Women Who Smoke Psychosom Med, October 1, 2008; 70(8): 928 - 935. [Abstract] [Full Text] [PDF]

				M. al'Absi, L. E. Wittmers, D. Ellestad, G. Nordehn, S. W. Kim, C. Kirschbaum, and J. E. Grant Sex Differences in Pain and Hypothalamic-Pituitary-Adrenocortical Responses to Opioid Blockade Psychosom Med, March 1, 2004; 66(2): 198 - 206. [Abstract] [Full Text] [PDF]

				D. Engler, E. Redei, and I. Kola The Corticotropin-Release Inhibitory Factor Hypothesis: A Review of the Evidence for the Existence of Inhibitory as Well as Stimulatory Hypophysiotropic Regulation of Adrenocorticotropin Secretion and Biosynthesis Endocr. Rev., August 1, 1999; 20(4): 460 - 500. [Abstract] [Full Text] [PDF]

				M. Korbonits, G. Kaltsas, L. A. Perry, P. Putignano, A. B. Grossman, G. M. Besser, and P. J. Trainer The Growth Hormone Secretagogue Hexarelin Stimulates the Hypothalamo-Pituitary-Adrenal Axis via Arginine Vasopressin J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2489 - 2495. [Abstract] [Full Text]

				J. Hangaard, M. Andersen, E. Grodum, O. Koldkjær, and C. Hagen The Effects of Endogenous Opioids and Cortisol on Thyrotropin and Prolactin Secretion in Patients with Addison's Disease J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1595 - 1601. [Abstract] [Full Text]

				G. S. Wand, D. Mangold, and M. Ali Adrenocorticotropin Responses to Naloxone in Sons of Alcohol-Dependent Men J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 64 - 68. [Abstract] [Full Text]

				G. S. Wand, D. Mangold, S. El Deiry, M. E. McCaul, and D. Hoover Family History of Alcoholism and Hypothalamic Opioidergic Activity Arch Gen Psychiatry, December 1, 1998; 55(12): 1114 - 1119. [Abstract] [Full Text] [PDF]

				G. S. Wand and H. Schumann Relationship between Plasma Adrenocorticotropin, Hypothalamic Opioid Tone, and Plasma Leptin J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2138 - 2142. [Abstract] [Full Text]