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Methylnaltrexone | CAS No: 916055-93-1 | GMP-certified suppliers
A medication that treats opioid-induced constipation in palliative care patients unresponsive to laxatives by selectively antagonizing peripheral opioid receptors without affecting central analgesia.
Therapeutic categories
Primary indications
- Treatment of opioids induced constipation in palliative patients that are inadequately responding to laxative therapy
Product Snapshot
- Methylnaltrexone is available as oral tablets and injectable solutions for subcutaneous administration
- It is primarily used to address opioid-induced constipation in patients unresponsive to laxative therapy
- The product holds regulatory approval in the US, Canada, and European Union markets
Clinical Overview
Pharmacologically, methylnaltrexone counteracts the opioid-induced reduction in gastrointestinal motility and transit time, which are commonly observed adverse effects of opioid analgesics. Unlike centrally acting opioid antagonists, methylnaltrexone’s quaternary ammonium structure restricts its ability to cross the blood-brain barrier, resulting in inhibition of peripheral μ-opioid receptors without reversing centrally mediated analgesia or precipitating opioid withdrawal symptoms.
Mechanistically, methylnaltrexone binds competitively to μ-opioid receptors localized in the gastrointestinal tract. This blockade alleviates opioid-induced delays in gastric emptying and bowel transit. Clinical pharmacodynamic studies have demonstrated that methylnaltrexone does not affect opioid-induced pupillary constriction, supporting its peripheral selectivity compared to non-selective antagonists such as naloxone.
Key absorption, distribution, metabolism, and excretion (ADME) properties reveal that methylnaltrexone is primarily renally excreted. It exhibits weak inhibition of the cytochrome P450 enzyme CYP2D6, which may have limited potential for drug interactions. Its phenanthrene-based chemical structure categorizes it within the class of polycyclic compounds derived from morphinans.
From a safety perspective, methylnaltrexone is generally well tolerated. Adverse effects are mostly gastrointestinal and consistent with its prokinetic activity. Because it does not cross the blood-brain barrier, the risk of central nervous system toxicity or opioid withdrawal is minimal.
Notable marketed formulations include injectable preparations designed for subcutaneous administration in clinical settings managing OIC. When sourcing methylnaltrexone API, quality assurance should focus on compliance with current Good Manufacturing Practice (cGMP) standards, ensuring the compound’s chemical purity, stereochemical integrity, and consistent pharmacological activity. Analytical characterization should confirm the quaternary ammonium nature that underpins its pharmacokinetic profile and peripheral receptor selectivity.
Identification & chemistry
| Generic name | Methylnaltrexone |
|---|---|
| Molecule type | Small molecule |
| CAS | 916055-93-1 |
| UNII | 0RK7M7IABE |
| DrugBank ID | DB06800 |
Pharmacology
| Summary | Methylnaltrexone is a peripherally acting μ-opioid receptor antagonist that counteracts opioid-induced gastrointestinal motility reduction without affecting central opioid receptors. It primarily targets μ- and κ-opioid receptors in the gastrointestinal tract to restore transit time. Its quaternary structure limits blood-brain barrier penetration, minimizing central nervous system effects. |
|---|---|
| Mechanism of action | Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing analgesic effects or withdrawal symptoms as it does not cross the blood-brain-barrier. |
| Pharmacodynamics | Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Mu-type opioid receptor | Humans | antagonist |
| Kappa-type opioid receptor | Humans | antagonist |
ADME / PK
| Absorption | Methylnaltrexone is rapidly absorbed. Tmax (SubQ): 30 minutes (regardless of dose); Cmax, 0.15 mg/kg SubQ dose = 117 ng/mL; AUC24, 0.15 mg/kg SubQ dose = 175 ng·hr/mL; |
|---|---|
| Half-life | terminal: 8.89 ± 2.59 h (intravenous) terminal: 6.14- 8.83 h (subcutaneous) |
| Protein binding | 11% to 15% bound to human plasma proteins. |
| Metabolism | 60% of the dose is metabolized. Conversion to methyl-6-naltrexol isomers (5% of total dose) and methylnaltrexone sulfate (1.3% of total dose) appear to be the primary pathways of metabolism. N‑demethylation of methylnaltrexone to produce naltrexone is not significant. |
| Route of elimination | Most of the drug is eliminated as unchanged drug (85% of administered radioactivity). Approximately half of the dose is excreted in the urine and somewhat less in feces. |
| Volume of distribution | Volume of distribution, steady state = 1.1 L/kg |
| Clearance | 10.5 ± 1.5 ml/min/kg (IV) |
Formulation & handling
- Methylnaltrexone is available for both oral and subcutaneous administration, with injectable forms predominating for rapid systemic delivery.
- The API is a small molecule with low water solubility and a negative LogP, indicating hydrophilic properties requiring appropriate formulation strategies for solution stability.
- Oral dosing requires administration on an empty stomach to avoid food interactions that may affect absorption and efficacy.
Regulatory status
| Lifecycle | The API is currently under patent protection in the United States until 2029-2030, with one patent expiring in 2024, and is marketed primarily in the US, Canada, and the EU. As key patents approach expiration in the coming years, the market is expected to transition toward increased generic competition. |
|---|
| Markets | US, Canada, EU |
|---|
Supply Chain
| Supply chain summary | Methylnaltrexone is primarily marketed under the branded product Relistor across the US, Canada, and EU markets. Multiple patents are held in the United States with expiry dates ranging from 2024 to 2030, indicating that some patent protection remains in place while others have or will soon lapse. The approaching patent expirations suggest potential for existing or upcoming generic competition in this API category. |
|---|
Safety
| Toxicity | LD50: 50 mg/kg (primates); Orthostatic hypotension at plasma levels in excess of 1.400 ng/mL. The most common (>5%) adverse reactions reported with methylnaltrexone bromide are abdominal pain, flatulence, nausea, dizziness, diarrhea and hyperhidrosis. |
|---|
- Toxicity data indicate an LD50 of 50 mg/kg in primates, signifying high acute toxicity potential
- Orthostatic hypotension observed at plasma concentrations exceeding 1,400 ng/mL
- Careful monitoring advised during handling to prevent exposure risks
Methylnaltrexone is a type of Opioid antagonists
Opioid antagonists are a crucial category of pharmaceutical active pharmaceutical ingredients (APIs) that play a vital role in the management and treatment of opioid-related disorders. These powerful substances bind to opioid receptors in the brain, blocking the effects of opioids and reversing their potentially life-threatening effects.
Opioid antagonists work by competitively binding to opioid receptors, preventing opioids from attaching to these receptors and inhibiting their activity. This mechanism of action effectively counteracts the effects of opioids, including pain relief, sedation, and respiratory depression. By blocking the receptors, opioid antagonists can rapidly reverse the effects of opioid overdose, providing a vital emergency intervention.
One of the widely used opioid antagonists is naloxone, a highly effective and fast-acting medication. Naloxone is commonly administered in emergency settings, such as hospitals and ambulances, as well as by first responders and bystanders. Its rapid onset of action and short duration make it an essential tool for reversing opioid overdoses, potentially saving lives.
Opioid antagonists not only serve as a critical intervention for overdose cases but also have applications in the management of opioid addiction. By blocking the rewarding effects of opioids, these pharmaceutical APIs can help reduce cravings and prevent relapse in individuals undergoing opioid dependence treatment.
In conclusion, opioid antagonists are indispensable pharmaceutical APIs in combating the devastating effects of opioids. Their ability to bind to opioid receptors and counteract the effects of opioids makes them essential in both emergency situations and addiction treatment. Naloxone, among other opioid antagonists, stands as a crucial tool in saving lives and addressing the opioid crisis.
Methylnaltrexone API manufacturers & distributors
Compare qualified Methylnaltrexone API suppliers worldwide. We currently have 3 companies offering Methylnaltrexone API, with manufacturing taking place in 3 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Chongqing Land Tower | Producer | China | China | CoA, USDMF | 5 products |
| Mallinckrodt | Producer | United States | Unknown | CoA, USDMF | 34 products |
| Noramco | Producer | United States | United States | CoA, USDMF | 18 products |
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