The following are all
μ-opioid receptor (MOR)
antagonists or
inverse agonists. Many of them also bind to the
κ-opioid receptor (KOR) and/or
δ-opioid receptor (DOR), where they variously behave as antagonists and/or agonists.
Centrally active These drugs are used mainly as
antidotes to reverse
opioid overdose and in the treatment of
alcohol dependence and
opioid dependence (by blocking the effects, namely
euphoria, of opioids so as to discourage
abuse).
Marketed •
Naloxone •
Naltrexone •
Nalmefene •
Samidorphan Diprenorphine is used in
veterinary medicine only.
Discontinued or rarely used •
Nalorphine •
Nalorphine dinicotinate •
Levallorphan Never marketed •
Nalodeine Peripherally restricted Peripherally acting μ-opioid receptor antagonists are used mainly in the treatment of
opioid-induced constipation. These are designed to specifically inhibit certain opioid receptors in the gastrointestinal tract and with limited ability to cross the blood–brain barrier. Therefore, they do not affect the analgesic effects of opioids within the central nervous system.
Marketed •
Alvimopan •
Methylnaltrexone •
Naloxegol •
Methylnaltrexone •
Naldemedine Under development currently or previously •
6β-Naltrexol •
Axelopran •
Bevenopran •
Methylsamidorphan Miscellaneous Buprenorphine and
dezocine are
partial agonists of the MOR but antagonists of the KOR. Contrarily,
eptazocine is an antagonist of the MOR but an agonist of the KOR; the same is also true for nalorphine and levallorphan. A variety of partial agonists or mixed agonists-antagonists of the MOR and KOR are also marketed, and include
butorphanol,
levorphanol,
nalbuphine,
pentazocine, and
phenazocine. All of the aforementioned drugs may be described as
opioid modulators instead of as pure antagonists. With the sole exception of nalorphine, all of the preceding are used as analgesics (by virtue of the fact that both MOR and KOR agonism independently confer pain relief). However, these opioid analgesics have atypical properties in comparison to the prototypical pure MOR full agonist opioid analgesics, such as less or no risk of
respiratory depression for MOR partial agonists and antagonists, reduced or no
euphoria,
abuse potential, and
dependence liability with MOR partial agonists/antagonists, and use- and dose-limiting
side effects such as
dysphoria and
hallucinations with KOR agonists. In addition, by virtue of its KOR antagonism, buprenorphine (as
buprenorphine/samidorphan (ALKS-5461) or
buprenorphine/naltrexone to block its MOR agonism) is under investigation for the treatment of
depression and
cocaine dependence, as are other KOR antagonists such as
aticaprant and, previously,
JDTic and
PF-4455242 (both discontinued due to
toxicity concerns). ==Selective antagonists==