Determination of receptors that mediate opiate side effects in the mouse.
The effects of mu and kappa-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 mu-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 kappa-receptor agonists only produced opiate side-effects at doses between 29 and greater than 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 mu-receptor agonists may produce both their antinociceptive effects and opiate side-effects by interacting with the mu-receptor. The kappa-receptor agonists have previously been shown to produce antinociception via the kappa-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 mu-receptor or to some other non-specific action.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011957:Receptors, Opioid / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D012399:Rotation; D013623:Tail / Q000187:drug effects
D000700:Analgesics; D001549:Benzamides; D001575:Benzomorphans; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; C006215:AH 7921; C032478:MR 2034; D016314:Ethylketocyclazocine; C027248:bremazocine; D003496:Cyclazocine; D010423:Pentazocine