Mixed Opioid Agonist Antagonists or Partial Agonists

The mixed opioid agonist-antagonists are potent analgesics in opioid-naive patients but precipitate withdrawal in patients who are physically dependent on opi-oids. They are useful for the treatment of mild to moderate pain. They were developed to reduce the addiction potential of the opioids while retaining the analgesic potency of the drugs. Their analgesic effect is generally attributed to an interaction at the k- and to a lesser extent the ^-opioid receptor.

Interaction at the K-receptor increases the sedative effects of the drugs. The euphoric effects are due to interaction with the ^-receptor. The dysphoric and psy-chotomimetic side effects of the drugs are attributed to interaction at the a-receptor.

The mixed agonist-antagonists and partial agonists differ from morphine in that they (1) produce excita-

tory and hallucinogenic effects, (2) produce a low degree of physical dependence, (3) induce withdrawal signs that differ from those of morphine, and (4) produce excitatory effects related to the sympathetic discharge of norepinephrine and therefore are positive inotropic agents in the heart.

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