Methylnaltrexone (MNTX, brand name Relistor), used in form of methylnaltrexone bromide (INN, USAN, BAN), is a medication that acts as a peripherally acting μ-opioid receptor antagonist that acts to reverse some of the side effects of opioid drugs such as constipation without significantly affecting pain relief or precipitating withdrawals. Because MNTX is a quaternary ammonium cation, it cannot cross the blood–brain barrier, and so has antagonist effects throughout the body, counteracting effects such as itching and constipation, but without affecting opioid effects in the brain such as pain relief. However, since a significant fraction (up to 60%) of opioid analgesia can be mediated by opioid receptors on peripheral sensory neurons, particularly in inflammatory conditions such as arthritis, traumatic or surgical pain, MNTX may increase pain under such circumstances. Medical uses
Methylnaltrexone is approved for the treatment of opioid-induced constipation in chronic non cancer pain or when ordinary laxatives have failed. Mechanism of action
Methylnaltrexone is a peripheral acting mu-opioid receptor antagonist, and does not cross the blood brain barrier. Methylnaltrexone has restricted access through the blood brain barrier because it is a quaternary amine, which carries a positive charge when in a solution and more has polarity with lower lipid solubility than a lot of the opioid agonists used for pain treatment. The peripheral action of methylnaltrexone makes it effective for decreasing the constipating effects of opioids, without interfering with the analgesic effects (of opioids) on the central nervous system.
Methylnaltrexone is being developed in subcutaneous and oral forms to treat opioid induced constipation (OIC). The use of methylnaltrexone (Relistor) for more than 4 months has not been studied. Society and culture
Approval
On April 1, 2008, Progenics and Wyeth announced that Health Canada has approved methylnaltrexone for the treatment of opioid-induced constipation. It was later approved by the US FDA on April 24, 2008. Forms
As of 2010, methylnaltrexone is supplied as an injection in trays containing seven one-dose vials containing 0.6 mL of solution. Each tray also contains seven 12 mm (0.47 in) 1 mL 27 gauge needles with retractable tips, and alcohol wipes for home use. A single vial can treat someone who weighs as much as 115 kilograms (254 lb). For hospital use, vials are available separately. See also
Loperamide - an μ-opioid receptor agonist that doesnt cross the BBB in significant amounts, and treats diarrhea (in contrast to methynaltrexone, a Mu-opioid receptor antagonist that doesnt cross the BBB, avoiding opiate withdrawal effects in patients, while treating constipation)
Naloxegol (trade names Movantik and Moventig) - another peripherally selective opioid antagonist used to treat opioid-induced constipation
(+)-Naloxone - a non-opioid drug which also reduces some side effects of opioids without significantly affecting analgesia when used in small oral doses
6β-Naltrexol (6α-hydroxynaltrexone) - another naltrexone derivative that is also a peripherally selective opioid antagonist

References


== Further reading ==