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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Influence of asimadoline, a new kappa-opioid receptor agonist, on tubular water absorption and vasopressin secretion in man.

AIMS: The purpose of the study was to investigate the effects of asimadoline, a new kappa-opioid agonist, on renal function and on hormones related to body fluid balance as well as its tolerability in healthy subjects. METHODS: In a placebo-controlled, randomised, double-blind crossover design we studied the effects of single oral doses of 1, 5, and 10 mg of asimadoline, in 24 healthy volunteers. Two hour control urine collections were followed by 2 h postdose urine collections and subsequently 2.5% saline was given i.v. at a rate of 0.3 ml min(-1) kg(-1) during another 2 h urine collection. Blood was obtained hourly. Arginine-vasopressin ( AVP), atrial natriuretic peptide (alpha-hANP), endothelin (ET-1) and cAMP were determined by r.i.a. or ELISA. RESULTS: GC-MS measurements revealed Cmax values of asimadoline in plasma ranging from 18 ng ml(-1) at the 1 mg dose, 91 ng ml(-1) at the 5 mg dose, to 214 ng ml(-1) at the 10 mg dose after an average of 1.1-1.4 h. Without effects on blood pressure, heart rate, GFR or urine electrolyte excretion, urine volume increased after 1-2 h after administration of 5 and 10 mg asimadoline from 3.3+/-1.3 to 5.6+/-1.4 (P<0.05) and from 3.2 +/-1.6 to 5.5+/-2.2 ml min(-1) (P<0.01), respectively. CH2O rose from 0.2+/-1.5 to 2.0+/-1.6 (P<0.05) and from 0.6+/-1.6 to 3.0+/-1.6 ml min(-1) (P<0.01). Urinary excretion of AVP was suppressed only with the 10 mg dose from 46+/-23 to 25+/-15 fmol min(-1) (P<0.05) without and from 410+/-206 to 181+/-125 fmol min(-1) (P<0.05) with stimulation by 2.5% saline. Plasma AVP was suppressed only by the 10 mg dose of asimadoline in six of eight subjects during the 2.5% saline infusion. Changes in the alpha-hANP or ET-1 systems were not affected by asimadoline. CONCLUSIONS: Asimadoline is diuretic in man after single doses of 5 or 10 mg probably through a direct effect at the renal tubular level. Suppression of AVP secretion was observed only at the highest dose level of 10 mg of asimadoline.[1]


  1. Influence of asimadoline, a new kappa-opioid receptor agonist, on tubular water absorption and vasopressin secretion in man. Kramer, H.J., Uhl, W., Ladstetter, B., Bäcker, A. British journal of clinical pharmacology. (2000) [Pubmed]
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