Antinociception produced by oral, subcutaneous or intrathecal administration of SC-39566, an opioid dipeptide arylalkylamide, in the rodent

Donna L Hammond; Awilda Stapelfeld; Edward J Drower; Michael A Savage; Linda Tam; Robert H Mazur

doi:10.1016/S0022-3565(25)38979-2

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Antinociception produced by oral, subcutaneous or intrathecal administration of SC-39566, an opioid dipeptide arylalkylamide, in the rodent

Journal article

Peer reviewed

Antinociception produced by oral, subcutaneous or intrathecal administration of SC-39566, an opioid dipeptide arylalkylamide, in the rodent

Donna L Hammond, Awilda Stapelfeld, Edward J Drower, Michael A Savage, Linda Tam and Robert H Mazur

The Journal of pharmacology and experimental therapeutics, Vol.268(2), pp.607-615

02/1994

DOI: 10.1016/S0022-3565(25)38979-2

PMID: 8113971

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Abstract

This study characterized the prototypic "minimum structure" enkephalin SC-39566 [2,6-dimethyl-L-tyrosinyl-D-alanine-(3-phenyl-1-propyl)-amide hydrochloride]. SC-39566 bound with highest affinity to mu opioid receptors (Ki, 0.13 nM), as well as to delta (Ki, 4.0 nM) opioid receptors in the rat brain, and with much lower affinity to kappa opioid receptors (Ki, 83.8 nM) in the guinea pig brain. In the mouse, SC-39566 inhibited phenylbenzoquinone-induced writhing and increased tail-flick and hot-plate latencies in a dose-dependent manner after either s.c. or p.o. (i.g.; intragastrical) administration. This antinociception was antagonized by the opioid antagonist naloxone, but not by alpha adrenergic, serotonergic, histaminergic, muscarinic cholinergic or dopaminergic receptor antagonists. In the rat, SC-39566 dose-dependently inhibited acetic-acid-induced writhing after s.c. or i.g. administration and increased response latencies in the tail-flick and hot-plate test after s.c. or intrathecal (i.t.) administration. The increase in tail-flick latency produced by s.c. SC-39566 in the rat was antagonized by s.c. naloxone with an apparent pA2 value of 7.9. Pretreatment with naltrindole, a delta opioid receptor antagonist, increased the ED50 of SC-39566 by only 1.7-fold. In addition, the increase in tail-flick latency produced by i.t. SC-39566 was not antagonized by i.t. administration of naltrindole or nor-binaltorphimine, a kappa receptor antagonist. These data suggest that the antinociceptive activity of SC-39566 is mediated predominantly by mu opioid receptors.

Injections, Spinal

Analgesics - pharmacology

Guinea Pigs

Administration, Oral

Dipeptides - pharmacology

Rats

Male

Receptors, Opioid, delta - drug effects

Rats, Sprague-Dawley

Mice, Inbred ICR

Dipeptides - administration & dosage

Receptors, Opioid, kappa - drug effects

Animals

Time Factors

Injections, Subcutaneous

Mice

Radioligand Assay

Details

Title: Subtitle: Antinociception produced by oral, subcutaneous or intrathecal administration of SC-39566, an opioid dipeptide arylalkylamide, in the rodent
Creators: Donna L Hammond - Department of Anesthesia and Critical Care, University of Chicago, Illinois
Awilda Stapelfeld
Edward J Drower
Michael A Savage
Linda Tam
Robert H Mazur
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.268(2), pp.607-615
Publisher: United States
DOI: 10.1016/S0022-3565(25)38979-2
PMID: 8113971
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: DA06736 / NIDA NIH HHS
Language: English
Date published: 02/1994
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984006302902771

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