G. Horvath et al., The synergistic antinociceptive interactions of endomorphin-1 with dexmedetomidine and/or S(+)-ketamine in rats, ANESTH ANAL, 93(4), 2001, pp. 1018-1024
Citations number
33
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Spinal administration of the endogenous mu -opioid agonist peptide, endomor
phin-1, results in antinociception in rodents, but there are few data about
its interaction with other antinociceptive drugs. We investigated the anti
nociceptive interactions at the spinal level of endomorphin-1 with the N-me
thyl-D-aspartate antagonist S(+)-ketamine, the alpha (2)-adrenoceptor agoni
st dexmedetomidine, or both in awake rats. Nociception was assessed by the
tail-flick test. Dose-response curves were determined for endomorphin-1 (0.
6-50 mug), for dexmedetomidine (0.1-10 mug), for mixtures of S(+)-ketamine
(30 or 100 mug) with endomorphin-1 (2-18 Ao,) or of endomorphin-1 with dexm
edetomidine in a fixed ratio (4:1), and for the triple combination of the t
hree drugs after intrathecal administration. Endomorphin-1 and dexmedetomid
ine both produced dose-dependent antinociception. The coadministration of 1
00 mug S(+)-ketamine significantly enhanced the antinociceptive effect of 6
mug endomorphin-1. Isobolographic analysis of the combinations of endomorp
hin-1 and dexmedetomidine revealed a synergistic interaction between these
drugs. The 80% effective dose for the triple combination was significantly
less than that for either binary combination. These data indicate that S(+)
-ketamine and dexmedetomidine, acting via different receptors, produce syne
rgistic antinociceptive interaction with endomorphin-1 at the spinal level.
Furthermore, the triple combination of an opioid agonist, an ar adrenocept
or agonist, and an N-methyl-D-aspartate receptor antagonist shows potent an
tinociceptive activity.