Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans
by
Walsh SL, Strain EC, Abreu ME, Bigelow GE.
Department of Psychiatry and Behavioral Sciences,
Johns Hopkins University School of Medicine,
Baltimore, MD 21224, USA.
swalsh@jhmi.edu
Psychopharmacology (Berl) 2001 Sep;157(2):151-62

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 humans. METHODS: Pilot evaluation (n=3) served to establish intramuscular doses of enadoline (20, 40, 80, and 160 microg/70 kg), butorphanol (1.5, 3, 6, and 12 mg/70 kg), and hydromorphone (1.5, 3, and 6 mg/70 kg) of comparable activity. These acute doses were examined under double-blind, placebo-controlled and constrained randomized conditions with a minimum of 72 h between tests in volunteers with polysubstance abuse histories (n=6). Physiological and subject- and observer-rated measures were collected 30 min before and for 4 h after administration. RESULTS: Enadoline significantly increased measures of sedation, confusion and dizziness, produced visual distortions and feelings of depersonalization, and increased urinary output. The highest dose (160 microg/70 kg) was not tolerated and led to psychotomimetic effects. Hydromorphone produced prototypic mu opioid effects including respiratory depression, miosis, and euphoria. Butorphanol was most similar to hydromorphone and shared few effects with enadoline. CONCLUSIONS: These results are discussed with respect to the potential use and safety of kappa agonists for clinical indications.

Mu
Pain
JDTIc
Kappa
Tramadol
Tolerance
Butorphanol
Endomorphins
Buprenorphine
Hydromorphone
Receptor subtypes
Nor-binaltorphimine
Fentanyl and ketamine
Kappa upregulation and addiction
Kappa opioids selectively control dopaminergic neurons
Depressive effects of the kappa-opioid receptor agonists
Kappa opioid antagonists as antidepressants: norbinaltorphimine
The kappa receptor antagonist norbinaltorphimine as an antidepressant

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