The effects of idazoxan and other alpha 2-adrenoceptor antagonists on urine output in the rat.
1. In normally-hydrated Wistar rats the alpha 2-adrenoceptor antagonist, idazoxan (1, 3, 10 mg kg-1 i.p.), increased urine output during the 6 h following injection. 2. The more selective and specific alpha 2-adrenoceptor antagonist, RX811059 (0.3, 1, 3 mg kg-1 i.p.), and the peripherally-acting alpha 2-adrenoceptor antagonist, L-659,066 (1, 3, 10 mg kg-1 i.p.), had no effect on urine output in normally-hydrated animals. 3. In rats given a 25 ml kg-1 water-load orally, idazoxan (10 mg kg-1, i.p.) produced an initial antidiuretic response which was followed by an increase in urine output which was apparent 4 and 6 h after drug administration. 4. RX811059 (1, 3 mg kg-1 i.p.) and L-659,066 (3, 10 mg kg-1 i.p.) significantly decreased urine output in water-loaded rats in the 2 h after injection. 5. The antidiuretic effects of L-659,066 were attenuated in Brattleboro rats which are deficient in vasopressin; only the highest dose (10 mg kg-1 i.p.) decreased urine output, and this was only a small response in comparison with its virtual abolition of urine output in water-loaded Wistar rats. 6. The results with the selective alpha 2-adrenoceptor antagonists in Wistar and Brattleboro rats suggest that alpha 2-adrenoceptors in the periphery may play a physiological role in the control of water balance through a mechanism which involves vasopressin. 7. The paradoxical diuretic effects of idazoxan contrast with the effects of the other alpha 2-adrenoceptor antagonists and therefore may be attributed to a property of this compound unrelated to alpha 2-adrenoceptor blockade.
Jackson
H C
HC
Reckitt & Colman Psychopharmacology Unit, Department of Pharmacology, School of Medical Sciences, University Walk, Bristol.
Griffin
I J
IJ
Birkett
S D
SD
Nutt
D J
DJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D019329:Idazoxan / Q000031:analogs & derivatives; D008297:Male; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D011910:Rats, Brattleboro; D017208:Rats, Wistar; D014563:Urodynamics / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011807:Quinolizines; D015016:Yohimbine; C055732:vatinoxan; C065483:ethoxyidazoxan; D019329:Idazoxan