A novel phencyclidine analog interacts selectively with Mu opioid receptors

Yossef Itzhak, E. J. Simon

Research output: Contribution to journalArticle

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Abstract

A new potent analgesic drug, 1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol (PCP-4-Ph-4-OH), derived from phencyclidine was tested for is 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-4-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.

Original languageEnglish
Pages (from-to)383-386
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume230
Issue number2
StatePublished - Jan 1 1984
Externally publishedYes

Fingerprint

Phencyclidine
mu Opioid Receptor
Inhibitory Concentration 50
Naloxone
Guinea Pigs
Dihydromorphine
Radioligand Assay
Vas Deferens
Enkephalins
Opioid Receptors
1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol
Ileum
Opioid Analgesics
Analgesics
Binding Sites
Membranes
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

A novel phencyclidine analog interacts selectively with Mu opioid receptors. / Itzhak, Yossef; Simon, E. J.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 230, No. 2, 01.01.1984, p. 383-386.

Research output: Contribution to journalArticle

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