Comparative Effects and Analgesic Efficacy of the Agonist-Antagonist Opioids

Pentazocine, butorphanol, nalbuphine, and buprenorphine are mixed agonist-antagonist opioids that are effective analgesics, with less abuse potential than the agonists morphine, propoxyphene, and codeine. The dual properties of the agonist-antagonists are largely explained by their varying actions at the postulated three types (μ, κ, and σ) of opioid receptors. The agonist-antagonists are classified as either morphine-like or nalorphine-like, based on their acute effects and withdrawal symptoms after chronic dosing. Buprenorphine is morphine-like, while the other drugs are nalorphine-like. These agents vary in the duration of analgesia, with pentazocine having a mean action of three hours and buprenorphine greater than six hours. The hemodynamic effects of nalbuphine and buprenorphine generally resemble those of morphine, while pentazocine and butorphanol increase cardiac workload, blood pressure, and pulmonary artery pressure. The agonist-antagonists have ceilings for respiratory depression, whereas the agonists produce dose-dependent depression. Agonist-antagonists generally produce less increase in biliary ductal pressure than does morphine. The major clinical limitations are that agonist-dependent patients may experience unpleasant subjective effects, when treated with the agonist-antagonists, and the nalorphine-like agents can produce psychotomimetic effects. More clinical experience is needed to rank the abuse potential within this group of opioids. The newer agents are being studied for oral use in acute and chronic pain.