- A PAMORA9
- An opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid receptors9
- Designed to have reduced ability to cross the blood–brain barrier, thereby limiting its potential to interfere with centrally mediated opioid analgesia9
Only OIC therapy with a strong recommendation and high quality of evidence from the American Gastroenterological Association.10
SYMPROIC® mechanism of action
Watch the video below to learn how SYMPROIC® may decrease the constipating effects of opioids.
This video is a visual representation of the SYMPROIC® (naldemedine) Mechanism of Action.
This video is not intended to represent the efficacy or safety shown in clinical trials.
Naldemedine, the active ingredient in SYMPROIC is a peripherally acting mu-opioid receptor antagonist, or PAMORA, that is approved for the treatment of opioid-induced constipation, OIC, in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
Naldemedine is derived from naltrexone, which has been modified to include an added side chain, which increases the molecular weight and polar surface area, to reduce its ability to cross the blood-brain barrier. Naldemedine is also a substrate of the P-glycoprotein (PgP) efflux transporter. Becauseit has a reduced ability to cross the blood-brain barrier central nervous system penetration of nalmededine is expected to be negligible at the recommended dose levels, limiting the potential to interference with centrally mediated opioid analgesics. Naldemedine is designed to inhibit the peripheral effects of opioid medications by blocking their actions at opioid receptors such as those myenteric and submucosal plexuses of the enteric nervous system (ENS) within the GI tract.
Naldemedine binds to the mu-opioid receptors located on motor neurons and secretomotor neurons within the ENS. It antagonizes the mu-opoioid receptor mediated changes in neurotransmitter release. Thereby blocking the inhibitory effect of opioids on GI motility and secretions. This leads to the decrease in the constipating effects of opioids.