Determination of receptors that mediate opiate side effects in the mouse

Abstract

The effects of μ and κ‐opiate receptor agonists were studied in a variety of tests in the mouse designed to correspond to clinical side‐effects in man. These included sedation, decrease in pupil diameter, Straub tail, decrease in body temperature, decrease in respiratory rate and inhibition of gut propulsion. The μ‐receptor agonists tested produced opiate side‐effects in the mouse at doses between 2.4 and 34 times higher than their antinociceptive doses in the abdominal constriction test. Their ranked orders of potency in producing these effects were very similar to their order of antinociceptive potency. In contrast, the κ‐receptor agonists only produced opiate side‐effects at doses between 29 and >2500 times higher than their antinociceptive doses. There was no correlation between the potency ratios in these tests and in the abdominal constriction test. It is concluded that μ‐receptor agonists may produce both their antinociceptive effects and opiate side‐effects by interacting with the μ‐receptor. The κ‐receptor agonists have previously been shown to produce antinociception via the κ‐receptor, but the opiate‐like side‐effects which appear with some of the drugs at much higher doses are probably due either to interaction with the μ‐receptor or to some other non‐specific action. 1983 British Pharmacological Society