Stereospecific increase by narcotic antagonists of evoked acetylcholine output in guinea-pig ileum.

In the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum, naloxone (30–100 nM) increases the output of acetylcholine evoked by electrical field stimulation at 0.017 Hz and to a lesser extent also at 10 Hz. The stereospecific requirements for this effect were studied with three pairs of optical isomers of antagonists of the benzomorphan series. The (−)-isomer of β-9-methyl-5-phenyl-2-allyl-2′-hydroxy-6,7-benzomorphan (GPA 1843) which had no agonist activity, had an effect similar to naloxone whereas the (+)-isomer was inactive in this respect. The (−)-isomer of antagonists with even weak agonist activity gave variable results. It is assumed that naloxone antagonises the action of enkephalin which has been shown to be present in the guinea-pig ileum. It is recommended to establish the stereospecificity of an antagonist action in order to exclude pharmacological effects not due to interaction with opiate receptors.