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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-2-6
pubmed:abstractText
The ability of a mixed CCKA/B receptor antagonist PD 142898 (benzenebutanic acid, beta-[[3-(1 H-indol-3-yl)-2-methyl-2-[[[(2-methyl- cyclohexyl)oxy]carbonyl]amino]-1-oxopropyl]amino]-[1 S-[1 alpha [S*(R*)]-2 beta]]) to modulate the antinociceptive, positive reinforcing and gastrointestinal actions of morphine was investigated in the rat. PD 142898 antagonised the development and maintenance of morphine (2.0 mg/kg, s.c.) induced conditioned place preference at 0.1 mg/kg, i.p. However, it potentiated the antinociceptive action of a subthreshold dose of morphine in the radiant tail flick model at doses of 0.001 and 0.01 mg/kg, s.c. Furthermore, PD 142898 (0.0001-1.0 mg/kg, s.c.) also potentiated the antinociceptive action of morphine (1.0 mg/kg, s.c.) against the late phase of formalin response associated with inflammation at the dose of 0.001-1.0 mg/kg. PD 142898 (0.001 mg/kg, s.c.) blocked the development of tolerance to morphine in the formalin test. It failed (0.001-1.0 mg/kg, i.p.) to modulate the inhibitory action of morphine (5.0 mg/kg, s.c.) on gastrointestinal transit as measured using the charcoal meal test. It is argued that the effect of PD 142898 in the conditioned place preference test involves antagonism of CCKA receptors, whilst the potentiation of the antinociceptive action of morphine is mediated via blockade of CCKB receptors. These results suggest that the mixed CCKA/B receptor antagonist may potentiate the analgesic action of morphine, block the development of tolerance without a concomitant increase in constipation and may also reduce the abuse potential of the opiate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
307
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
283-9
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Modulation of the in vivo actions of morphine by the mixed CCKA/B receptor antagonist PD 142898.
pubmed:affiliation
Department of Biology, Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, UK.
pubmed:publicationType
Journal Article