Thirty minutes after s.c. administration to rats of 0.15-10 mg/kg morphine or 0.005-5 of the enkephalin-like peptide FK 33-824, gastrointestinal transit of a forced charcoal meal was inhibited with closely comparable potency at the higher doses producing major effects; however, considerably less (about 100 times) FK 33-824 than morphine was sufficient to elicit threshold and even substantial (over 50%) inhibition. The marked transit inhibition (to less than 40% of control) caused by a small i.p. dose (0.04 mg/kg) of either drug was prevented almost completely in rats pretreated with the N-methyl quaternary analog of naloxone (1 mg/kg i.p.). Gastrointestinal transit and nociceptive reaction (jumping) to the hot-plate (55°C), were blocked in rats given i.v. 2.5 mg/kg FK 33-824 or double this dose of morphine; pretreatment with 1 mg/kg naloxone i.p. fully prevented both effects of morphine and antinociception by FK 33-824 whose intestinal action, however, was only partially antagonized. Morphine-induced inhibition of gastrointestinal transit was substantially reversed but there was no impairment of the drug's antinociceptive action when naloxone was replaced with its N-methyl quaternary analog (4 mg/kg), which under the same conditions did not affect FK 33-824's efficacy on these two endpoints. These results indicate that FK 33-824 has potent opiate-like action on gastrointestinal transit in rats and that, unlike naloxone, its N-methyl quaternary analog can selectively prevent morphine's effect on the gut without affecting antinociception.
|Number of pages||11|
|Journal||Research Communications in Substances of Abuse|
|Publication status||Published - 1981|
ASJC Scopus subject areas
- Medicine (miscellaneous)