Ohmefentanyl--a new agonist for mu-opiate receptor.
Ohmefentanyl (F 7302, N[1-(beta-hydroxy-beta-phenylethyl)-3-methyl-4-piperidyl]-N -phenylpropionamide) is a potent synthetic analgesic agent. The analgesic activity of ohmefentanyl in mice is 6300 times more potent than that of morphine. The potency of ohmefentanyl in competing with specific binding of 3H-naloxone is reduced by Na+ (100 mM) and GTP (50 microM), thus suggesting the agonist properties of this compound. Binding characteristics of 3H-ohmefentanyl with mice brain P2 fraction are studied. An important saturable, specific and reversible binding is demonstrated. Scatchard analysis indicates the existence of two classes of binding sites (KD1 = 0.32nM, KD2 = 3.91nM). Various opiate drugs strongly inhibit the binding of 3H-ohmefentanyl, but nonopiate drugs have negligible affinity. Comparison of the relative potencies of morphine, DSTLE(Tyr-D-Ser-Gly-Phe-Leu-Thr, a specific ligand for the delta-opiate receptor) and ohmefentanyl in competing with 3H-dihydromorphine (mu) and 3H-[D-Ala2, D-Leu5]-enkephalin (delta) binding to crude synaptic plasma membranes of mice brain shows that the inhibitory potencies of morphine, DSTLE and ohmefentanyl on 3H-DHM binding are 79, 0.11 and 81.5 times those on 3H-DADLE binding respectively. This suggests that ohmefentanyl has potent mu-agonist properties.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D000700:Analgesics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C037016:F 7302; D005283:Fentanyl