TY - JOUR
T1 - Enadoline, a selective kappa opioid agonist
T2 - Comparison with butorphanol and hydromorphone in humans
AU - Walsh, S. L.
AU - Strain, E. C.
AU - Abreu, M. E.
AU - Bigelow, G. E.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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 μg/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 μg/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.
AB - 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 μg/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 μg/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.
KW - Butorphanol
KW - CI-977
KW - Enadoline
KW - Human
KW - Hydromorphone
KW - Kappa opioid
KW - Mixed agonist-antagonist
KW - Mu opioid
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U2 - 10.1007/s002130100788
DO - 10.1007/s002130100788
M3 - Article
C2 - 11594439
AN - SCOPUS:0034873586
VL - 157
SP - 151
EP - 162
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 2
ER -