Abstract

It has been found that the previously inactive narcoticantagonist analgesics become active in the mouse tail-flick test in the presence of physostigmine. Physostigmine itself and the centrally acting cholinergic agent oxotremorine are potent inhibitors of this reflex. Naloxone, a pure narcotic antagonist, can block the effects of physostigmine and oxotremorine. The narcotic-antagonist analgesics also block the contractions of the isolated coaxially stimulated guinea-pig ileum. In a wide variety of narcotic antagonists, a high correlation has been found between the activity of these compounds in this test procedure and their potency as analgesics in man. These results are discussed in support of the hypothesis that cholinergic systems may be involved in the analgesic action of these drugs.