Evaluation of the receptor selectivities of opioid drugs by investigating the block of their effect on urine output by beta-funaltrexamine.
The effects of a series of opioid drugs on urine output in the water-loaded rat were studied and also the block of those effects by the irreversible opioid receptor antagonist, beta-funaltrexamine (beta-FNA). Fentanyl, d-propoxyphene, profadol, bromadoline, buprenorphine and nalbuphine produced only a decrease in urine output, which was antagonised by pretreatment with beta-FNA, 40 mg/kg s.c., 24 hr beforehand. These drugs were thus characterized as selective mu receptor agonists. U-50,488, tifluadom, Mr2034, proxorphan, ethylketocyclazocine and butorphanol all produced an initial decrease in urine output, which was antagonized by beta-FNA, and therefore probably mu receptor mediated, followed by a beta-FNA insensitive diuretic effect, which was probably kappa receptor mediated. For U-50,488, tifluadom, Mr2034 and proxorphan the threshold dose for increasing urine output was lower than that for decreasing it, suggesting that these four compounds are kappa-selective agonists. For ethylketocyclazocine and butorphanol, the threshold doses for producing both effects were similar, suggesting that these two drugs are non-selective agonists. SKF 10,047 produced a diuretic effect at low dose-levels, which may be kappa receptor mediated, and a beta-FNA insensitive decrease in urine output at higher dose-levels, which may suggest a sigma receptor mediated effect.
D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; C024524:beta-funaltrexamine