Subclasses of opioids based on body temperature change in rats: acute subcutaneous administration

Morphine and a number of opioid agonists and agonist-antagonists were injected into rats to examine their effects on body temperature after acute systemic administration. Dose- and time-response curves were constructed for each drug alone and in the presence of the antagonist naloxone. Based on these data, the opioids could be subdivided into several groups. The first group, made up of morphine, heroin, l-methadone, etorphine, fentanyl and levorphanol, caused hyperthermia at lower doses and hypothermia at higher ones. Both effects could be blocked by naloxone. A second group, consisting of buprenorphine, nalbuphine and l-pentazocine, produced only a naloxone-sensitive increase in body temperature, whereas the group comprising ethylketazocine, ketazocine, l-cyclazocine and normeperidine caused only a decrease. This fall in temperature was relatively less sensitive to naloxone blockade. Still another group of drugs (meperidine, normorphine and d-pentazocine) had little effect themselves but, in combination with naloxone, induced hypothermia. The fifth group (N-allylnormetazocine, d-cyclazocine, dextrorphan and d-methadone) had no effect whether alone or in the presence of the antagonist. These findings can be explained in terms of a two-receptor model by ascribing distinct thermoregulatory functions to each receptor type.