Interactions of drugs active at opiate receptors and drugs active at alpha 2-receptors on various test systems.

1 The actions of the opiate receptor drugs, morphine, methionine-enkephalin (Met-enkephalin) and naloxone were compared with the actions of the alpha 2-receptor drugs, clonidine, xylazine and yohimbine on analgesic tests, in vitro bioassay (guinea-pig ileum and mouse vas deferens), and radioligand displacement studies on rat brain membrane preparations. 2. Both opiate and alpha 2-agonist drugs showed analgesic activity but whilst the alpha 2-agonist analgesic activity was antagonized by only alpha 2-antagonists, the analgesic activity of morphine was antagonized by both naloxone and yohimbine. In the in vitro tests, both groups of agonists inhibited electrically evoked activity; however in these experiments only antagonism of opiates by naloxone and alpha 2-agonists by yohimbine could be shown and it is concluded that in these systems the activity of the alpha 2-agonists is mediated via the presynaptic alpha 2-receptors only. 3 In the radioligand studies the drugs acting at alpha 2-receptors were active in the micromolar range at displacing labelled opioid ligands but opiates did not displace labelled alpha 2-ligands. 4 It is concluded that drugs which act on alpha 2-receptors interfere with the in vivo analgesic effects of opiates and weakly displace opioid radioligand binding, but opioids do not affect alpha 2 agonist analgesia and do not appear to displace alpha 2-agonist radioligand binding.