The Opioid Receptor Like-1 Receptor Agonist Ro 64-6198 (1S,3aS-8-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one) Produces a Discriminative Stimulus in Rats Distinct from That of a μ, κ, and δ Opioid Receptor Agonist Cue

@article{Recker2004TheOR,
  title={The Opioid Receptor Like-1 Receptor Agonist Ro 64-6198 (1S,3aS-8-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one) Produces a Discriminative Stimulus in Rats Distinct from That of a $\mu$, $\kappa$, and $\delta$ Opioid Receptor Agonist Cue},
  author={Matthew D Recker and Guy A Higgins},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2004},
  volume={311},
  pages={652 - 658}
}
Male Wistar rats were trained to discriminate either the opioid receptor like (ORL)-1 receptor agonist Ro 64-6198 (1S,3aS-8-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one) or morphine from saline using a two-choice, food reinforced, operant procedure. Acquisition of Ro 64-6198 discrimination was relatively slow (mean trials to criterion 113 ± 6), and a final 4 mg/kg dose (initial training dose 2 mg/kg) was required to establish appropriate stimulus control… 

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References

SHOWING 1-10 OF 47 REFERENCES

Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function

In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist.

A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.

These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphan in F Q/nOCiceptin in adaptive behavioral fear responses to stress.

Probes for Narcotic Receptor Mediated Phenomena

The synthesis of a series of epoxy 5-phenylmorphans is being explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan molecule that may be needed both

U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist.

It is suggested that different opioid receptors mediate the analgesic effects of morphine and U-50,488, a more selective kappa agonist that causes opioid receptor-mediated sedation, diuresis and corticosteroid elevations.

Discriminative stimulus properties of U50,488 and morphine: effects of training dose on stimulus substitution patterns produced by mu and kappa opioid agonists.

It is indicated that training dose is an important determinant of the different levels of cross-substitution obtained between mu and kappa agonists, and that a greater pharmacological specificity of drug-induced discriminative stimuli can be obtained when relatively high training doses of mu andKappa opioid agonists are used to establish the discrimination.

The nociceptin receptor as a potential target in drug design.

A review of the recent exciting progress in this field compares the actions of OP(4) agonists and antagonists with those of classic opioids, and seeks to predict some of the untoward effects that may be seen with such drugs.

The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats

It is shown here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine induced a pronounced CPP, suggesting that this new class of anxiolytic drugs is devoid of the risk for potential non-medical use and dependence.

Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans

The pharmacodynamic effects of enadoline significantly increased measures of sedation, confusion and dizziness, produced visual distortions and feelings of depersonalization, and increased urinary output, and the highest dose was not tolerated and led to psychotomimetic effects.