A comparison of the antinociceptive actions of cholinomimetic and morphine-like drugs.

1. The antinociceptive activity of morphine, nalorphine, oxotremorine and eserine has been examined in mice in electroshock and phenylbenzoquinone writhing tests.2. The effectiveness of these drugs alone, in combination with each other, and in combination with the muscarinic antagonist atropine sulphate, and with the narcotic antagonist naloxone has also been investigated.3. In both tests morphine was effective and antagonized by naloxone.4. Nalorphine was active in the phenylbenzoquinone test but only slightly active in the electroshock test: it was antagonized by naloxone in both tests.5. Morphine was potentiated by nalorphine in the phenylbenzoquinone test. but antagonized by it in the electroshock test.6. Oxotremorine was effective in both tests, and was antagonized by atropine sulphate.7. Eserine was active only in the phenylbenzoquinone test, and was antagonized by atropine sulphate.8. Oxotremorine was potentiated by eserine in the phenylbenzoquinone test, but antagonized by it in the electroshock test.9. Crossed agonist and partial agonist experiments produced enhancement.10. No antagonism was seen in the crossed antagonist experiments.11. The similarities between the effects of the two classes of drugs are discussed, and the conclusion drawn that they act by separate mechanisms.