H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors

NIDA Res Monogr. 1986:75:209-12.

Abstract

H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) exhibited high affinity (IC50 = 2.80 nM) in displacing [3H]naloxone binding (nH = 0.89 +/- 0.1) and showed an exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50(naloxone) ratio of 4,840, while it displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM) in rat brain binding assays. [3H]CTOP was recently custom synthesized (spec. act.: 84 Ci/mmol) and evaluated for its in vitro binding properties towards the mu opioid receptors in rat brain membrane preparations. Association and dissociation of [3H]CTOP binding to mu opioid receptors were rapid at 25 degrees C with a kinetic Kd value of 0.67 nM. Saturation experiments gave apparent Kd value of 1.11 nM and Bmax value of 136 +/- 13 fmol/mg prot at 25 degrees C. Specific [3H]CTOP binding was inhibited by a number of different opioid and opiate ligands. Among them, putative mu opioid receptor-specific ligands, such as naloxone, naltrexone and CTOP inhibited the binding with high affinity, while delta opioid receptor-specific compounds or non-opioid drugs inhibited specific [3H]CTOP binding with low affinity or they were ineffective.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / metabolism
  • Kinetics
  • Naloxone / metabolism
  • Rats
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology

Substances

  • Enkephalins
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
  • Naloxone
  • Somatostatin
  • Enkephalin, D-Penicillamine (2,5)-