Naloxazone
Encyclopedia
Naloxazone is an irreversible μ opioid receptor
antagonist
which is selective for the μ1 receptor subtype. Naloxazone produces very long lasting antagonist effects as it forms a covalent bond
to the active site of the mu-opioid receptor, thus making it impossible for the molecule to unbind and blocking the receptor permanently until the receptor is recycled by endocytosis
.
It has been reported that naloxazone is unstable in acidic solution, dimerizing into the more stable and much more potent antagonist naloxonazine
. Under conditions in which no naloxonazine formation could be detected, naloxazone did not display irreversible μ opioid receptor binding.
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
which is selective for the μ1 receptor subtype. Naloxazone produces very long lasting antagonist effects as it forms a covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
to the active site of the mu-opioid receptor, thus making it impossible for the molecule to unbind and blocking the receptor permanently until the receptor is recycled by endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
.
It has been reported that naloxazone is unstable in acidic solution, dimerizing into the more stable and much more potent antagonist naloxonazine
Naloxonazine
Naloxonazine is a potent irreversible mu opioid antagonist. Naloxonazine forms spontaneously in acidic solutions of naloxazone, and may be responsible for much or all of the irreversible μ opioid receptor binding displayed by the latter.-See also:...
. Under conditions in which no naloxonazine formation could be detected, naloxazone did not display irreversible μ opioid receptor binding.
See also
- ChlornaltrexamineChlornaltrexamineChlornaltrexamine is an irreversible mixed agonist-antagonist for μ-opioid receptors, which forms a covalent bond to the active site. It is 22 times more potent than morphine...
, an irreversible mixed agonist-antagonist - OxymorphazoneOxymorphazoneOxymorphazone is an opioid analgesic drug related to oxymorphone. Oxymorphazone is a potent and long acting μ-opioid agonist which binds irreversibly to the receptor, forming a covalent bond which prevents it from detaching once bound...
, an irreversible μ-opioid full agonist