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

@article{Walsh2001EnadolineAS,
  title={Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans},
  author={Sharon L. Walsh and Eric C. Strain and Mary E. Abreu and George E. Bigelow},
  journal={Psychopharmacology},
  year={2001},
  volume={157},
  pages={151-162}
}
Abstract. Rationale: The availability of the highly selective and specific kappa opioid agonist enadoline provides an opportunity to explore the function of kappa receptors in humans and their potential utility as a target for substance abuse pharmacotherapy development. Objectives: The purpose of this study was to characterize the pharmacodynamic effects of enadoline, a selective kappa agonist, and to compare it with butorphanol, a mixed mu/kappa agonist, and hydromorphone, a mu agonist, in… 
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References

SHOWING 1-10 OF 55 REFERENCES
Differential naltrexone antagonism of hydromorphone and pentazocine effects in human volunteers.
  • K. Preston, G. Bigelow
  • Psychology, Biology
    The Journal of pharmacology and experimental therapeutics
  • 1993
TLDR
Differential blockade of mu-like and kappa-like opioid effects by naltrexone was demonstrated in human subjects and the results suggest that mu agonist activity may suppress kappa -like effects such a dysphoria.
kappa-Opioid receptor effects of butorphanol in rhesus monkeys.
TLDR
The results of this investigation are consistent with an in vivo agonist activity of butorphanol at kappa-opioid receptors that can only be demonstrated when an insurmountable antagonist has substantially eliminated the dominant receptor population through which it exerts its action.
The pharmacology of butorphanol, a 3,14-dihydroxymorphinan narcotic antagonist analgesic.
TLDR
Butorphanol, a new, totally synthetic morphinan, which is chemically related to naloxone, has been demonstrated to have both analgesic and narcotic antagonist properties and showed weak to moderate central depressant properties at doses which were considerably higher than those producing analgesia.
The antinociceptive activity of kappa- but not delta-opioid receptor agonists is maintained in morphine-tolerant neuropathic rats.
TLDR
In mononeuropathic rats, morphine pretreatment results in cross-tolerance to delta- but not to kappa-opioid receptor agonists, which is suggested to be a sign of chronic constriction of the common sciatic nerve.
Discrimination of butorphanol and nalbuphine in opioid-dependent humans
Butorphanol, levallorphan, nalbuphine and nalorphine as antagonists in the squirrel monkey.
  • L. Dykstra
  • Psychology
    The Journal of pharmacology and experimental therapeutics
  • 1990
The effects of several mixed-action opioid agonist/antagonists were examined alone and in combination with the mu-opioid agonist l-methadone and the kappa-opioid agonist,
Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo.
TLDR
Ketocyclazocine is different from morphine-like agonists in that it produces only minimal miosis and lacks euphoriant action, and causes a dysphoric state and was clearly discriminated from morphine.
Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans.
TLDR
The data do not support the use of naltrexone as a treatment for cocaine abuse, but suggest it may be useful for treating patients with concurrent cocaine and heroin abuse.
...
...