A CLASSIFICATION OF OPIATE RECEPTORS THAT MEDIATE ANTINOCICEPTION IN ANIMALS

TLDR

The study aimed to identify which opiate receptors mediate antinociception by evaluating opioid analgesic activity against various nociceptive stimuli in mice and rats. Researchers measured the activity profiles of opioid analgesics across different nociceptive tests in mice and rats. μ‑opioid agonists produced steep, parallel dose‑response curves and maximal effects in heat tests, with potency ratios similar to human analgesia, whereas κ‑agonists were inactive in heat tests except at sedative doses; however, both μ‑ and κ‑agonists elicited steep, parallel dose‑response curves in writhing and paw‑pressure tests, demonstrating that both receptor types mediate antinociception in animals.

Abstract

To investigate the opiate receptors that mediate antinociception, the activity profiles of opioid analgesic drugs have been determined against different nociceptive stimuli in the mouse and rat. In tests that employ heat as the nociceptive stimulus, μ‐opiate receptor agonists, such as morphine, pethidine and dextropropoxyphene, had steep and parallel dose‐response curves and were capable of achieving maximum effects. In addition, the antinociceptive potency ratios of these drugs in heat tests were similar to those for analgesia in man. The κ‐agonists, such as ethylketazocine, nalorphine, Mr2034 and pentazocine, were essentially inactive against heat nociception except at doses that caused sedation and motor incapacitation. In the writhing and paw pressure tests both μ‐ and κ‐agonists produced steep and parallel dose‐response curves. It is concluded that both μ‐ and κ‐opiate receptors mediate antinociception in animals and that the interactions of analgesic drugs with these receptors may be classified in terms of their antinociceptive activities against qualitatively different nociceptive stimuli.