Antidiuretic effect of bremazocine and U-50,488 in rats after alpha 2-adrenoceptor blockade.
The role of alpha 2-adrenoceptors and kappa-opioid receptors in urination was studied in rats. In water-loaded rats (40 mL kg-1 p.o.) the kappa-opioid agonist bremazocine (0.05 0.2 mg kg-1 i.p.) induced a dose-related diuretic response in the second hour after administration, but had no effect in the first hour. When rats were pretreated with the alpha 2-adrenoceptor antagonist idazoxan (1 mg kg-1 s.c.), bremazocine induced a dose-related antidiuretic response in the first hour; thereafter the rats showed an increase of urination similar to that with bremazocine alone. The antidiuretic effect of bremazocine was dependent on the dose of idazoxan with maximal response after 1-3 mg kg-1. Similar results were obtained with bremazocine in the presence of yohimbine (1 mg kg-1 s.c.). The antidiuretic profile of bremazocine after idazoxan was shared by U-50,488 (2.5-10 mg kg-1 i.p.), although this compound alone at the high dose reduces urine output in the first hour. The antidiuresis induced by bremazocine in the presence of idazoxan in water-loaded rats was completely antagonized by 10 but not 2 mg kg-1 i.p. of the opioid antagonist naloxone. Thus, kappa-opioid agonists, in addition to their diuretic effect, also produce an antidiuretic response which may be mediated by alpha 2-adrenoceptors.
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001575:Benzomorphans; D004146:Dioxanes; D011759:Pyrrolidines; D015016:Yohimbine; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C027248:bremazocine; D019329:Idazoxan