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

作者：Jacobs G E^*; Hulskotte E G J; van Gerven J M A; Zuurman L; de Kam M L; Elassaiss Schaap J; Ruigt G; van Pelt J; Peeters B W M M; Peeters P A M; Burggraaf J

来源：Journal of Psychopharmacology, 2011, 25(3): 353-360.

DOI：10.1177/0269881109358203

• desmopressin
• hypothalamus-pituitary-adrenal axis
• vasopressin
• function test
• challenge
• stress related psychopathology

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 mu g bolus (over 1 min) or a 30 mu g 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 mu g dDAVP bolus and the 30 mu g incremental infusion, while cardiovascular and coagulatory effects were greater with the 30 mu g dose. Osmolality and ANS activity remained uninfluenced. AEs corresponded to dDAVP's side-effect profile. In conclusion, the neuroendocrine effects of a 10 mu g dDAVP bolus administered over 1 min are similar to those of a 30 mu g incremental infusion administered over one hour, despite higher dDAVP concentrations after the infusion. Cardiovascular and coagulatory effects showed clear dose-related responses. A 10 mu g dDAVP bolus is considered a safe vasopressinergic function test at which no confounding effects of systemic or autonomic stress were seen.

• 出版日期2011-3