Filters
Custom request?
Type
Production region
Qualifications
Country of origin
Milnacipran API Manufacturers & Suppliers
14 verified results
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Commercial-scale Suppliers
Employees: 25
All certificates
Employees: 19
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
All certificates
Total market transparency
Supplier trade data access
Buyer / supplier flow comparison
Milnacipran | CAS No: 92623-85-3 | GMP-certified suppliers
A medication that manages fibromyalgia and major depressive disorder in adults by selectively inhibiting serotonin and norepinephrine reuptake to relieve pain and mood symptoms.
Therapeutic categories
Primary indications
- Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the management of fibromyalgia in patients that are 18 years old or above
- While milnacipran may be used for the treatment of major depressive disorder (MDD), it is only recommended in adult patients who are 18 years old or above due to an increased risk for suicidal ideation, thinking, and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders
- Some regional prescribing information notes that the use of the medication is specifically for the short-term symptomatic relief of MDD
- Nevertheless, it is important to note that the regulatory approval of and/or indications listed here for milnacipran may or may not exist and/or vary greatly between regions and nations [F3928, F3934]
Product Snapshot
- Milnacipran is available as oral capsules and film-coated tablets, categorized as an oral small molecule
- Its primary therapeutic uses include the management of fibromyalgia and short-term symptomatic relief of major depressive disorder in adults
- The product has US FDA approval status for indicated uses and remains investigational in other regulatory contexts
Clinical Overview
Pharmacologically, milnacipran exhibits a relatively balanced inhibition of serotonin (5-HT) and norepinephrine (NE) reuptake, with a somewhat greater preference for norepinephrine. This dual reuptake inhibition enhances the synaptic availability of these neurotransmitters, which is believed to underlie its therapeutic effects in both fibromyalgia and MDD. In fibromyalgia, modulation of descending inhibitory pain pathways via increased NE and 5-HT is thought to contribute to analgesic effects, while in MDD, enhanced neurotransmission of NE and 5-HT addresses symptoms related to mood, alertness, and energy.
Pharmacokinetic and safety data indicate that milnacipran is generally well tolerated but can cause increases in heart rate and blood pressure at therapeutic and supratherapeutic doses. ECG studies demonstrate no clinically significant prolongation of the QT interval, although mean heart rate increases up to ~20 bpm and blood pressure elevations in the range of 3.8 to 10.6 mmHg have been observed. Milnacipran does not significantly interact with a wide range of neurotransmitter receptors or ion channels, nor does it inhibit monoamine oxidases or acetylcholinesterase.
Of note, ongoing investigational research on the levorotatory enantiomer, levomilnacipran, suggests potential BACE-1 enzyme inhibition, implicating possible future applications in Alzheimer’s disease, though this remains experimental.
From a sourcing and quality perspective, the procurement of milnacipran API should ensure compliance with stringent purity and stereochemical specifications due to the importance of its enantiomeric composition for pharmacological activity. Suppliers must provide detailed characterization data and adhere to regional pharmacopeial standards where applicable to support regulatory submissions and maintain consistent clinical performance.
Identification & chemistry
| Generic name | Milnacipran |
|---|---|
| Molecule type | Small molecule |
| CAS | 92623-85-3 |
| UNII | G56VK1HF36 |
| DrugBank ID | DB04896 |
Pharmacology
| Summary | Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that increases synaptic concentrations of these monoamines by inhibiting their transporters. Its dual modulation of serotonin and norepinephrine is implicated in alleviating pain through descending inhibitory pathways, supporting its use in fibromyalgia, and in regulating mood and cognitive symptoms associated with major depressive disorder (MDD). Milnacipran demonstrates no significant affinity for other neurotransmitter receptors or ion channels, indicating a targeted pharmacodynamic profile. |
|---|---|
| Mechanism of action | The dual ability for milnacipran to inhibit the reuptake of both serotonin (5HT) and norepinephrine (NE) facilitates its treatment of both fibromyalgia and major depressive disorder (MDD). In particular, it is generally believed that 5HT and NE participate in the modulation of endogenous analgesic mechanisms by way of the descending inhibitory pain pathways in the brain and spinal cord [A175759, A175843, A175846]. Although the specific mechanism of action remains unclear, some studies have proposed that low levels of 5HT may be associated with increased sensitivity to pain - a condition that could subsequently be improved by milnacipran's capacity to enhance the presence of 5HT by inhibiting its reuptake via serotonin transporters at synaptic clefts [A175846, F3937, L5659]. Furthermore, in the CNS it is also generally believed that NE released from descending pathways can mitigate pain sensations via eliciting inhibitory effects on alpha-2A-adrenoceptors on central terminals of primary afferent nociceptors, by direct alpha-2-adrenergic action on pain-relay neurons, and by alpha-1-adrenoceptor-mediated activation of inhibitory interneurons . Such NE pain mitigation is consequently also enhanced by milnacipran's ability to enhance the presence of NE by inhibiting its reuptake via norepinephrine transporters at synaptic clefts . Concurrently, milnacipran's capacity to inhibit the reuptake of both 5HT and NE also facilitates its treatment of MDD. Given the monoamine hypothesis' assertion that decreased 5HT can be associated with anxiety, obsessions, compulsions, and decreased NE can result in lowered alertness, energy, attention, and general interest in life, it is proposed that milnacipran's basic activities as a serotonin and norepinephrine reuptake inhibitor could assist in treating such symptoms of MDD by increasing the presence of both 5HT and NE in the body by inhibiting their reuptake . |
| Pharmacodynamics | When utilized to treat fibromyalgia, the effect of milnacipran on the QTcF interval in patients was measured in a double-blind placebo-and positive-controlled parallel study in 88 healthy subjects using three to six times the recommended therapeutic dose for fibromyalgia at 600 mg/day . After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms - an increase that is generally not considered to be clinically significant . Conversely, when used for treating major depressive disorder (MDD), non-clinical studies have shown that levomilnacipran binds with high affinity to the norepinephrine (NE) and serotonin (5-HT) transporters (Ki = 71-91 nM and 11 nM respectively at human transporters) [F3919, F3922, F3925]. Levomilnacipran inhibits the uptake of both NE and 5-HT in vitro and in vivo; preferentially inhibiting reuptake of NE over 5-HT by approximately 2-fold [F3919, F3922, F3925]. Levomilnacipran does not directly affect the uptake of dopamine or other neurotransmitters [F3919, F3922, F3925]. Levomilnacipran has no significant affinity for serotonergic (5-HT1-7), α- and β-adrenergic, muscarinic (M1-5), histamine (H1-4), dopamine (D1-5), opiate, benzodiazepine, and γ-aminobutyric acid (GABA) receptors in vitro [F3919, F3922]. Levomilnacipran has no significant affinity for Ca++, K+, Na+, and Cl– channels and does not inhibit the activity of human monoamine oxidases (MAO-A and MAO-B) or acetylcholinesterase [F3919, F3922, F3925]. Moreover, in ECG studies with levomilnacipran used to treat MDD, although no clinically significant changes in QTcF interval (QTcF=QT/RR0.33) were noted, it appears that the agent can cause increases in heart rate and blood pressure . In particular, it appears that the maximum therapeutic dose of levomilnacipran at 120 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 20.2 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 3.8 to 7.2 mmHg and 6.1 to 8.1 mmHg, respectively . Alternatively, a supratherapeutic dose of 300 mg/day is capable of causing a maximum mean difference in heart rate from placebo of 22.1 bpm and a mean difference in systolic and diastolic blood pressure from placebo ranging from 5.4 to 7.9 mmHg and 7.9 to 10.6 mmHg, respectively . |
Targets
| Target | Organism | Actions |
|---|---|---|
| Sodium-dependent serotonin transporter | Humans | inhibitor |
| Sodium-dependent noradrenaline transporter | Humans | inhibitor |
| NMDA receptor | Humans | inhibitor |
ADME / PK
| Absorption | Racemic milnacipram demonstrates an absolute bioavailability of about 85-90% following oral administration . Maximum concentrations of the racemic agent are reached within 2-4 hours after oral dosing, and steady-state levels are obtained by 36-48 hours . Conversely, the relative bioavailability of levomilnacipram has been documented as 92% [F3919, F3922]. The median time to peak concentration Tmax for levomilnacipram is about 6-8 hours after oral administration [F3919, F3922]. After daily dosing of levomilnacipram 120 mg, the mean Cmax value is 341 ng/mL, and the mean steady-state AUC value is 5196 ng.h/mL. In general, the administration of either racemic milnacipram or levomilnacipram with food does not affect the medication's oral bioavailability [F3925, F3919, F3922]. |
|---|---|
| Half-life | The terminal elimination half-life documented for racemic milnacipran is approximately 6-8 hours, where d-milnacipran has a longer elimination half-life of 8-10 hours compared to that of the l-enantionmer at 4-6 hours . Alternatively, the terminal elimination half-life determined specifically for levomilnacipran formulations is about 12 hours [F3919, F3922]. |
| Protein binding | The protein binding determined for racemic milnacipran is 13% . Conversely, the plasma protein binding documented for levomilnacipran is 22% over a concentration range of 10 to 1000 ng/mL [F3919, F3922]. |
| Metabolism | It has been determined that levomilnacipran undergoes desethylation and hydroxylation to generate desethyl levomilnacipran and p-hydroxy-levomilnacipran, respectively [F3919, F3922, A175897]. Both oxidative metabolites undergo further conjugation with glucuronide to form the conjugate milnacipran carbamoyl-O-glucuronide [F3919, F3922, F3925, A175897]. The desethylation is catalyzed primarily by CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2 [F3919, F3922]. Additionally, it is the general understanding that there is no interconversion between the enantiomers of milnacipran in the body [F3919, F3922, F3925, F3928]. |
| Route of elimination | Levomilnacipran and its metabolites are eliminated primarily by renal excretion [F3919, F3922]. Following oral administration of 14C-levomilnacipran solution, approximately 58% of the dose is excreted in urine as unchanged levomilnacipran [F3919, F3922]. N-desethyl levomilnacipran is the major metabolite excreted in the urine and accounted for approximately 18% of the dose [F3919, F3922]. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxy levomilnacipran (1%) [F3919, F3922]. |
| Volume of distribution | The mean volume of distribution recorded for racemic milnacipran following a single intravenous dose to healthy subjects was approximately 400 L . Alternatively, levomilnacipran is widely distributed with an apparent volume of distribution of 387-473 L [F3919, F3922]. |
| Clearance | The total plasma clearance determined for milnacipran is approximately 40 L/h . |
Formulation & handling
- Milnacipran is a small molecule API formulated exclusively for oral administration in tablet and capsule forms.
- It has moderate water solubility and a LogP value indicating balanced hydrophilic-lipophilic properties suitable for oral dosing.
- Formulations should consider patient tolerability by allowing administration with or without food, while avoiding concurrent excessive alcohol use due to potential liver effects.
Regulatory status
| Lifecycle | The active pharmaceutical ingredient is marketed primarily in the United States, with key patents expiring between 2021 and 2023, while one patent remains in force until 2029, indicating a transition towards increased generic availability in the near term. |
|---|
| Markets | US |
|---|
Supply Chain
| Supply chain summary | The manufacturing and supply landscape for Milnacipran involves several packagers primarily serving the US market. The originator branded product, including Savella, has a presence mainly in the United States, with no indications of marketed products in the EU or other regions. Several US patents remain active, with expiration dates ranging up to 2029, indicating limited generic competition currently available or anticipated in the near term. |
|---|
Safety
| Toxicity | There is limited clinical experience with milnacipran overdose in humans. In clinical trials, cases of acute ingestions up to 1000 mg daily were reported with none being fatal . In postmarketing experience, fatal outcomes have been reported for acute overdoses primarily involving multiple drugs but also with milnacipran only . The most common signs and symptoms of overdose included increased blood pressure, cardio-respiratory arrest, changes in the level of consciousness (ranging from somnolence to coma), confusional state, dizziness, and increased hepatic enzymes [F3919, F3922, F3925]. There are no adequate and well-controlled studies in pregnant women [F3919, F3922, F3925]. In fact, milnacipram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [F3919, F3922, F3925]. Neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding [F3919, F3922, F3925]. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying [F3919, F3922, F3925]. These features are consistent with either a direct toxic effect of SNRI class drugs like milnacipran or, possibly, a drug discontinuation syndrome [F3919, F3922, F3925]. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [F3919, F3922, F3925]. The effect of milnacipran on labor and delivery in humans is unknown [F3919, F3922, F3925]. Milnacipran should be used during labor and delivery only if the potential benefits outweigh the potential risks [F3919, F3922, F3925]. There are no adequate and well-controlled studies in nursing mothers [F3919, F3922, F3925]. It is not known if milnacipran is excreted in human milk [F3919, F3922, F3925]. Studies have shown that levomilnacipran is excreted into the milk of lactating rats [F3919, F3922, F3925]. Subsequently, possible excretion into human milk possesses the potential for serious adverse reactions in nursing infants [F3919, F3922, F3925]. As a consequence, breastfeeding by women treated with levomilnacipran should be considered only if the potential benefits outweigh the potential risks to the child [F3919, F3922, F3925]. Milnacipran is not indicated for use in children under 18 years of age due to concerns over the potential for agitation-type emotional and behavioral changes, as well as suicidal ideation and/or behavior [F3919, F3922, F3925]. SNRIs like milnacipran have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [F3919, F3922, F3925]. Levomilnacipran was not mutagenic when evaluated in vitro in a bacterial mutagenicity study (Ames test) and not genotoxic in a mouse lymphoma study [F3919, F3922, F3925]. It was not clastogenic in an in vivo micronucleus assay in rats [F3919, F3922, F3925]. The potential effects of levomilnacipran on gonadal function, mating behavior, reproductive performance and early pregnancy were evaluated in rats at oral doses of 0, 10, 30, or 100 mg/kg/day [F3919, F3922, F3925]. The NOAEL was 100 mg/kg/day based on reductions in body weight gain and food consumption [F3919, F3922, F3925]. There were no levomilnacipran effects on male and female fertility parameters [F3919, F3922, F3925]. In the rat and rabbit embryo/fetal development studies, decreases in maternal body weight gain and food consumption were noted [F3919, F3922, F3925]. In the fetuses, increases in the incidence of ossification anomalies were noted but were of no toxicological significance [F3919, F3922, F3925]. In both species, the NOAEL was determined to be 100 mg/kg/day, a dose which represents a rat or rabbit animal-to-human exposure margin of 9-fold and 4-fold, respectively relative to the human exposure from 120 mg/day of levomilnacipran [F3919, F3922, F3925]. Material safety data for milnacipran has documented the LD50 oral value in the rat model as being 213 mg/kg [MSDS]. |
|---|
- Acute overdose of milnacipran can result in elevated blood pressure, cardio-respiratory arrest, altered consciousness, confusional states, and elevated hepatic enzymes
- Fatalities have been reported primarily in multi-drug overdose scenarios
- Milnacipran is not established for use in pregnant or lactating women due to potential fetal/neonatal risks and unknown excretion in human milk
Milnacipran is a type of Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) belong to a vital subcategory of pharmaceutical active pharmaceutical ingredients (APIs) that have gained significant popularity in the treatment of various medical conditions. SNRIs work by modulating the levels of two essential neurotransmitters in the brain, namely serotonin and norepinephrine.
These APIs are commonly prescribed for managing a range of mental health disorders, including depression, anxiety disorders, and certain chronic pain conditions. By inhibiting the reuptake of serotonin and norepinephrine, SNRIs enhance their availability in the brain, leading to improved mood, increased energy levels, and reduced pain perception.
SNRIs exhibit a unique dual mechanism of action, making them distinct from other classes of antidepressant medications. By targeting both serotonin and norepinephrine reuptake, SNRIs provide a broader spectrum of therapeutic effects, making them effective in treating patients who do not respond well to other medications.
Due to their widespread usage and effectiveness, SNRIs have become a preferred choice for healthcare professionals. Some commonly prescribed SNRIs include duloxetine, venlafaxine, and desvenlafaxine. These APIs are typically available in oral formulations and are well-tolerated by most patients, with a favorable side effect profile.
In summary, SNRIs represent a significant subcategory of pharmaceutical APIs that play a crucial role in the management of mental health disorders and chronic pain conditions. Their unique dual mechanism of action and effectiveness make them a valuable treatment option for healthcare providers, ensuring improved patient outcomes and quality of life.
Milnacipran (Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)), classified under Antidepressants
Antidepressants are a category of pharmaceutical Active Pharmaceutical Ingredients (APIs) widely used in the treatment of depression and other mood disorders. These medications work by balancing the levels of certain chemicals in the brain called neurotransmitters, such as serotonin, norepinephrine, and dopamine.
There are several types of antidepressants available, each with its own mechanism of action and efficacy. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed as a first-line treatment for depression. They prevent the reabsorption of serotonin, resulting in increased serotonin levels in the brain. Examples of popular SSRIs include fluoxetine, sertraline, and escitalopram.
Tricyclic antidepressants (TCAs) are another class of antidepressants that work by blocking the reuptake of both serotonin and norepinephrine. They are generally used when SSRIs are ineffective or not well-tolerated. Amitriptyline, nortriptyline, and imipramine are commonly prescribed TCAs.
Other antidepressants include serotonin-norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, and monoamine oxidase inhibitors (MAOIs). SNRIs, such as venlafaxine and duloxetine, inhibit the reuptake of both serotonin and norepinephrine. Atypical antidepressants, including bupropion and mirtazapine, have diverse mechanisms of action, targeting multiple neurotransmitters. MAOIs, such as phenelzine and tranylcypromine, work by inhibiting the enzyme monoamine oxidase, which breaks down neurotransmitters.
It is important to note that antidepressants may have various side effects and require close monitoring by healthcare professionals. Dosages and treatment duration vary based on individual needs and response. Antidepressants are typically prescribed as part of a comprehensive treatment plan that may include psychotherapy and lifestyle modifications.
In conclusion, antidepressants are a vital category of pharmaceutical APIs used to manage depression and related mood disorders. They act on neurotransmitters in the brain to alleviate symptoms and improve overall well-being. It is crucial to consult with a healthcare provider to determine the most suitable antidepressant and monitor its effects.
Milnacipran API manufacturers & distributors
Compare qualified Milnacipran API suppliers worldwide. We currently have 14 companies offering Milnacipran API, with manufacturing taking place in 5 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 |
|---|---|---|---|---|---|
| Centaur Pharma | Producer | India | India | CoA, GMP, USDMF, WC | 40 products |
| Cosma | Producer | Italy | Italy | CoA, USDMF | 20 products |
| Derivados Quimicos | Producer | Spain | Spain | CoA, USDMF | 18 products |
| Global Pharma Tek | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, ISO9001, MSDS | 484 products |
| Hetero Labs | Producer | India | India | CoA, GMP, USDMF, WC | 90 products |
| Lupin | Producer | India | India | CoA, USDMF | 155 products |
| Micro Labs | Producer | India | India | CoA, GMP, WC | 38 products |
| MSN Pharma | Producer | India | India | CoA, GMP, USDMF, WC | 31 products |
| Mylan | Producer | India | India | CoA, GMP, USDMF, WC | 201 products |
| Pierre Fabre Medi. | Producer | France | France | CoA, JDMF, USDMF | 4 products |
| Raks Pharma | Producer | India | India | CoA, USDMF | 58 products |
| SETV Global | Producer | India | India | CoA, FDA, GMP | 515 products |
| Sumitomo Chemical | Producer | Japan | Japan | CoA, JDMF | 28 products |
| Unichem Labs. | Producer | India | India | CoA, USDMF | 62 products |
When sending a request, specify which Milnacipran API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Milnacipran API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
