Journal article
Selective antagonism by naltrindole of the antinociceptive effects of the delta opioid agonist cyclic[D-penicillamine2-D-penicillamine5]enkephalin in the rat
The Journal of pharmacology and experimental therapeutics, Vol.259(2), pp.725-731
11/1991
DOI: 10.1016/S0022-3565(25)20326-3
PMID: 1658309
Abstract
Spinal delta opioid receptors have been proposed to mediate antinociception in the rat on the basis of 1) the efficacy of a small number of agonists; 2) the lack of effect of mu-selective antagonists; and 3) the lack of cross-tolerance with mu-selective agonists. However, direct evidence to support or refute this postulate has not been obtained in the rat due to a lack of suitable delta-selective antagonists. The present study characterized the ability of Naltrindole (NTI, 17-cyclopropylmethyl-6,7-dehydro-4,5 alpha-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan), a recently discovered delta-selective antagonist, to antagonize the antinocieption produced by intrathecal (i.t.) administration of the prototypic delta-selective agonist cyclic[D-penicillamine2-D-penicillamine5]enkephalin (DPDPE) or the mu-selective agonists morphine and [D-Ala2,MePhe4,Gly-ol5] enkephalin (DAMGO) in the rat. Intrathecal coadministration of NTI with DPDPE significantly antagonized the increase in tail-flick latency (TFL) and hot-plate latency (HPL) produced by DPDPE. In the absence of NTI, the ED50 values and 95% CL of DPDPE in the tail-flick and hot-plate tests were 2.8 (1.1-4.7) and 19.5 (13.3-33.7) micrograms, respectively. In the presence of 10 micrograms of NTI, the ED50 value of DPDPE in the tail-flick test was unchanged and was increased by 2-fold in the hot-plate test to 35.9 (26.2-60.1) micrograms. In the presence of 30 micrograms of NTI, the ED50 value of DPDPE in the tail-flick test was increased by 5-fold to 14.5 (8.5-24.9) micrograms and its antinociceptive effect in the hot-plate test was antagonized completely.
Details
- Title: Subtitle
- Selective antagonism by naltrindole of the antinociceptive effects of the delta opioid agonist cyclic[D-penicillamine2-D-penicillamine5]enkephalin in the rat
- Creators
- Edward J Drower - Department of Central Nervous System Research, G.D. Searle & Co., Skokie, IllinoisAwilda StapelfeldMichael F RaffertyBrian R de CostaKenner C RiceDonna L Hammond
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.259(2), pp.725-731
- Publisher
- United States
- DOI
- 10.1016/S0022-3565(25)20326-3
- PMID
- 1658309
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Language
- English
- Date published
- 11/1991
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006412102771
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