A novel phencyclidine analog interacts selectively with mu opioid receptors.
A new potent analgesic drug, 1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol (PCP-4-Ph-4-OH), derived from phencyclidine was tested for its interactions with different types of opioid receptors. The antinociceptive effect of PCP-4-Ph-4-OH in the mouse writhing test (ED50 = 0.3 mg/kg) is reversed by low doses of naloxone (pA2 = 6.98). The potency of PCP-4-Ph-OH in the inhibition of the electrically induced contractions of the guinea-pig ileum (IC50 = 17 nM) is 8-fold higher than that in the mouse vas deferens preparation (IC50 = 130 nM). The concentration of naloxone required to double the IC50 (Ke) of PCP-4-Ph-4-OH is 1.5 to 1.9 nM in both preparations. In opioid radioreceptor assays, PCP-4-Ph-4-OH displays 60- to-300 fold higher affinity for the [3H] dihydromorphine (mu) and D-[3H]Ala2-MePhe-Gly-ol5-enkephalin (mu) binding sites than for D-[3H]Ala2-D-Leu5-enkephalin (delta) sites in rat brain and [3H]bremazocine (kappa) sites in guinea-pig cerebellar membrane preparations. These results suggest that PCP-4-Ph-4-OH interacts with high affinity and selectivity with mu opioid receptors.
D000698:Analgesia; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive; D002531:Cerebellum / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D014649:Vas Deferens / Q000187:drug effects
D001575:Benzomorphans; D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C042378:1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol; D004090:Dihydromorphine; C027248:bremazocine; D010622:Phencyclidine