Differential effects of fedotozine compared to other kappa agonists on diuresis in rats.
The aim of our study was to test the effect of fedotozine (0.1-30 mg/kg, s.c.), a novel kappa opioid agonist, on water diuresis in the conscious hydrated rat. Its effect was compared to that of morphine (2.5-10 mg/kg), a mu opioid agonist and to some of the recognized kappa agonists described in the literature: bremazocine (0.3-30 micrograms/kg), tifluadom (0.1-3 mg/kg), Cl 977 1-1000 micrograms/kg), (-)-cyclazocine (0.01-1 mg/kg), PD 117,302 (0.03-3 mg/kg), U-50,488h (0.25-10 mg/kg) and U-69,593 (0.3-3 mg/kg). The effect of fedotozine was also tested after intracerebroventricular administration (100 micrograms/kg) and compared to that of U-50,488h (10-30 micrograms) and dynorphins A(1-17), A(1-13) and B(1-13) (2.5-10 micrograms). All the reference kappa agonists administered by the s.c. route induced water diuresis, whereas morphine inhibited diuresis and electrolyte excretion. However, fedotozine (0.1-30 mg/kg s.c.) had no effect on diuresis, even after low doses of naloxone (0.1 mg/kg s.c.) or nor-BNI (10 mg/kg s.c.), and at 1 mg/kg had inconsistent effects on electrolyte elimination. When administered in the lateral ventricle of the brain, U-50,488h and dynorphin A(1-17) induced water diuresis, unlike fedotozine (100 micrograms), DYN A(1-13) and DYN B(1-13) that had no effect on urine output. Furthermore, fedotozine did not alter the diuretic effects of U-50,488h. These results suggest that fedotozine is an atypical kappa agonist, lacking activity on the kappa receptor subtypes regulating diuresis.
Soulard
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CD
Institut de Recherche Jouveinal, Fresnes, France.
Guerif
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S
Payne
A
A
Dahl
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SG
D000818:Animals; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D011437:Propylamines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D001593:Benzyl Compounds; D011437:Propylamines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C067749:fedotozine