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Desmopressin as a pharmacological tool in vasopressinergic hypothalamus-pituitary-adrenal axis modulation: neuroendocrine, cardiovascular and coagulatory effects.

Author(s): Jacobs GE, Hulskotte EG, van Gerven JM, Zuurman L, de Kam ML, Elassaiss-Schaap J, Ruigt G, van Pelt J, Peeters BW, Peeters PA, Burggraaf J

Affiliation(s): Centre for Human Drug Research, Leiden, The Netherlands.

Publication date & source: 2011-03, J Psychopharmacol., 25(3):353-60. Epub 2010 Feb 8.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Arginine-vasopressin (AVP) is a physiological co-activator of the hypothalamus-pituitary-adrenal (HPA) axis, together with corticotrophin releasing hormone (CRH). A synthetic analogue of AVP, desmopressin (dDAVP), is often used as a pharmacological tool to assess co-activation in health and disease. The relation between dDAVP's neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic and non-specific stress effects has not been studied. A randomized, double-blind, placebo-controlled, three-way crossover study was performed in 12 healthy male and female volunteers (6 : 6). dDAVP was administered intravenously as a 10 mug bolus (over 1 min) or a 30 mug incremental infusion (over 60 min). Neuroendocrine, cardiovascular, pro-coagulatory, anti-diuretic effects and adverse events (AEs) were recorded, and autonomic nervous system (ANS) activation evaluated. The incremental infusion reached 1.8-fold higher dDAVP concentrations than the bolus. Neuroendocrine effects were similar for the 10 mug dDAVP bolus and the 30 mug incremental infusion, while cardiovascular and coagulatory effects were greater with the 30 microg dose. Osmolality and ANS activity remained uninfluenced. AEs corresponded to dDAVP's side-effect profile. In conclusion, the neuroendocrine effects of a 10 mug dDAVP bolus administered over 1 min are similar to those of a 30 mug incremental infusion administered over one hour, despite higher dDAVP concentrations after the infusion. Cardiovascular and coagulatory effects showed clear dose-related responses. A 10 mug dDAVP bolus is considered a safe vasopressinergic function test at which no confounding effects of systemic or autonomic stress were seen.

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