Antagonism of morphine analgesia by CCK-8-S does not extend to all assays nor all opiate analgesics.
The conditions under which CCK-8-S may block opiate-induced analgesia were examined in detail. A U-shaped dose-response relationship was observed for the ability of CCK-8-S to attenuate (by approximately 50%, at most) morphine-induced tail flick analgesia. The analgesic effects of morphine in the hot plate or acetic acid-induced stretching tests were not altered by CCK-8-S at doses that antagonized morphine in the tail flick test. Tail flick latency elevations induced by meptazinol, a putative mu-1 receptor agonist, were also attenuated by CCK-8-S according to a U-shaped dose-response relationship, but those induced by U-50,488, a kappa agonist, were not antagonized by CCK-8-S doses that attenuated morphine analgesia. Thus, the ability of CCK-8-S to antagonize opiate analgesia does not follow a conventional dose-response relationship, does not extend to all tests of analgesia and may not extend to all opioid drugs. Analgesia mediated by the mu-1 opioid receptor subtype may be more amenable to antagonism by CCK-8-S than that mediated by the kappa receptor subtype.
Barbaz
B S
BS
Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Hall
N R
NR
Liebman
J M
JM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D008297:Male; D008621:Meptazinol / Q000494:pharmacology*; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology; D011759:Pyrrolidines / Q000494:pharmacology*; D012016:Reference Values; D012844:Sincalide / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013464:Sulfuric Acids / Q000494:pharmacology
D000700:Analgesics; D001381:Azepines; D011759:Pyrrolidines; D013464:Sulfuric Acids; D008621:Meptazinol; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D012844:Sincalide