The interaction of the two isomers of the opioid benzodiazepine tifluadom with mu-, delta-, and kappa-binding sites and their analgesic and intestinal effects in rats.
The (+) and (-) isomers of tifluadom were assessed in rats for their opioid activities. In vitro (+)-tifluadom was almost equipotent at mu- and kappa- sites and about 10 times less potent at delta-sites: (-)-tifluadom had the same binding spectrum but was 10-20 times less potent. In vivo (+)-tifluadom delayed the hot-plate reaction time; this effect was antagonized by naloxone, but not by Ro 15-1788. (-)-Tifluadom up to 20 mg/kg had no antinociceptive effect. In the intestinal transit test analgesic doses of (+)-tifluadom did not delay the intestinal transit of a charcoal meal in rats and had weak antagonist activity against morphine-induced inhibition of intestinal transit, whereas (-)-tifluadom had neither agonist nor antagonist effect. It thus appears that (+)-and (-)-tifluadom are not selective in vitro and in vivo for one type of opioid binding site/receptor.
Petrillo
P
P
Amato
M
M
Tavani
A
A
D000701:Analgesics, Opioid; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013237:Stereoisomerism
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001569:Benzodiazepines; C035470:tifluadom