INTERACTIONS OF DRUGS ACTIVE AT OPIATE RECEPTORS AND DRUGS ACTIVE AT α2‐RECEPTORS ON VARIOUS TEST SYSTEMS

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Abstract
1 The actions of the opiate receptor drugs, morphine, methionine-enkephalin (Met-enkephalin) and naloxone were compared with the actions of the α2-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 α2-agonist drugs showed analgesic activity but whilst the α2-agonist analgesic activity was antagonized by only α2-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 α2-agonists by yohimbine could be shown and it is concluded that in these systems the activity of the α2-agonists is mediated via the presynaptic α2-receptors only. 3 In the radioligand studies the drugs acting at α2-receptors were active in the micromolar range at displacing labelled opioid ligands but opiates did not displace labelled α2-ligands. 4 It is concluded that drugs which act on α2-receptors interfere with the in vivo analgesic effects of opiates and weakly displace opioid radioligand binding, but opioids do not affect α2 agonist analgesia and do not appear to displace α2-agonist radioligand binding.