Opioid Antagonists

Naloxone and naltrexone are pure opioid antagonists synthesized by relatively minor changes in the morphine structure. Alteration of the substituent on the piperidine nitrogen from a methyl group to a longer side chain changes the drug from an agonist to an antagonist.

Opioid antagonists bind to the opioid receptor with high affinity and have low efficacy. The pure antagonists block the effects of opioids at all opioid receptors. However, as previously discussed, the dose required for naloxone blockade of the ^-receptor versus the k-opioid receptor is several times as much. All opioid antagonists will precipitate withdrawal in opioid-depend-ent patients.

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