Methoclocinnamox ( MCCAM; developmental code name NIH-10420) is a selective pseudo-irreversible partial agonist of the μ-opioid receptor (MOR).
MCCAM was derived from clocinnamox (CCAM), was first described by 1995, and was of interest in the potential treatment of opioid dependence.
Pharmacology
Pharmacodynamics
MCCAM acts as a selective pseudo-irreversible
partial agonist of the μ-opioid receptor (MOR).
It shows both
opioid agonist- and antagonist-like effects in animals.
More specifically, it has
analgesic effects, mixed reinforcing effects, appears to lack significant respiratory depression, alleviates opioid withdrawal symptoms, and provides long-lasting blockade and protection against the effects of MOR
(including their reinforcing effects as well as their
toxic and
lethality effects, for instance in
opioid overdose).
Due to its pseudo-irreversible nature, MCCAM is insurmountable by conventional reversible MOR ligands, for instance
morphine,
alfentanil, and
naltrexone.
MCCAM is
buprenorphine-like in many regards, but differs from buprenorphine in its pseudo-irreversibility.
Pharmacokinetics
MCCAM is known to be partially metabolically converted into
clocinnamox (CCAM), a MOR pseudo-irreversible antagonist.
In monkeys, with oral administration of MCCAM, 70 to 80% of the drug is eliminated as conjugated CCAM, whereas with subcutaneous injection, up to 70% of the drug is
excretion unchanged.
As such, the
drug metabolism of MCCAM, and by extension its effects, differ by route of administration.
The metabolism of MCCAM also shows species differences between rodents and monkeys.
Chemistry
MCCAM, also known as
O-methylclocinnamox, is structurally related to the MOR irreversible antagonists
clocinnamox (CCAM) and
methocinnamox (MCAM).
CCAM and its analogues were derived by structural modification of
buprenorphine.
History
Clocinnamox (CCAM) was first described in the scientific literature by 1992.
MCCAM was first described by 1995.
It was developed by researchers at the National Institute on Drug Abuse (NIDA) of the
United States National Institutes of Health (NIH).
The drug was of interest in the possible treatment of opioid dependence.
However, it was never marketed.
(MCAM), a close analogue of MCCAM, was first described in 2000.
MCAM was under development for the treatment of opioid dependence and
opioid overdose by 2020.
