Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes

Y. Itzhak, J. M. Hiller, E. J. Simon

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42 Scopus citations


Binding of [3H](d)-N-allylnormetazocine ([3H](d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (B(max) = 260 fmol/mg of protein) and manifests moderately high affinity (K(d) = 20 nM). The rank order of potency among opioid-benzomorphans and phencyclidine (PCP) analogs for competition for [3H](d)-NANM-binding sites is as follows: (d)-NANM = PCP-3-OH > (d)-cyclazocine > N-ethylphenylcyclohexylamine > PCP > (l)-cyclazocine = dextrorphan > (d/l)-ethylketocyclazocine > (d/l)-bremazocine > (1)-NANM > 1-phenylcyclohexylamine > levorphanol. Other opioid ligands, relatively selective for each of the types of opioid binding sites other than σ, such as morphine (μ), H-Tyr-D-Ala(Me)Phe-NH-CH2-OH (μ), D-Ala2-D-Leu5-enkephalin (δ), tifluadom (κ), and U50488 (κ) as well as etorphine and naloxone were all unable to compete with [3H](d)-NANM for specific binding even at a concentration of 1 μM. Regional distribution studies of [3H](d)-NANM-binding sites show high density in the hippocampus, thalamus, hypothalamus, and amygdala and low density in cerebellum and nonfrontal neocortex membranes of the rat brain. These binding sites are very sensitive to protein-modifying enzymes and reagents such as trypsin and N-ethylmaleimide and to heat denaturation. These results provide direct biochemical evidence for the existence of distinct (d)-NANM-binding sites in rat brain. In addition, this study supports the view that PCP and several of its analogues and the dextrorotatory isomers of psychotomimetic benzomorphans may act at a common recognition site in rat central nervous system.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalMolecular Pharmacology
Issue number1
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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