Nomifensine is a synthetic isoquinoline derivative and monoamine reuptake inhibitor that was historically developed as an antidepressant. It primarily inhibits the reuptake of dopamine and norepinephrine, with weaker activity at serotonin transporters. Nomifensine is chemically classified as a substituted tetrahydroisoquinoline compound.
Nomifensine was formerly marketed mainly as its maleate salt. However, its medicinal use was discontinued because of serious safety concerns, particularly hemolytic anemia. The FDA records that the U.S. approval for Merital capsules was subsequently withdrawn. Therefore, current product-page content should present Nomifensine primarily in the context of pharmaceutical research, analytical reference work and chemical/API information, rather than as a currently approved therapeutic medicine.
Nomifensine is a specialized pharmaceutical compound relevant to analytical chemistry, pharmacological research and historical antidepressant research.
For pharmaceutical-grade material, important quality attributes include:
Because Nomifensine is no longer an approved marketed antidepressant in major regulatory markets, a current universal pharmacopoeial API release specification could not be verified. Numerical CMS limits should therefore not be invented and should be taken from the applicable validated specification or CoA.
Product Name: Nomifensine
CAS Number: 24526-64-5
Alternate CAS / Maleate: 32795-47-4
Molecular Formula: C16H18N2
Molecular Weight: 238.33 g/mol
Chemical Name: 2-Methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine
IUPAC Name: 2-Methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine
Drug Class: Monoamine Reuptake Inhibitor
Pharmacological Class: Norepinephrine-Dopamine Reuptake Inhibitor
Therapeutic Area: Central Nervous System / Psychiatry
Molecule Type: Synthetic Small Molecule
PubChem identifies Nomifensine with CAS 24526-64-5, molecular formula C16H18N2, and its molecular structure as 2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine.
Nomifensine was historically formulated as the maleate salt, which has a separate chemical identity.
Nomifensine Maleate CAS: 32795-47-4
Molecular Formula: C20H22N2O4
Molecular Weight: 354.40 g/mol
The maleate consists of Nomifensine combined with maleic acid in a 1:1 salt form.
This distinction is important when preparing an API page because Nomifensine base and Nomifensine maleate should not be treated as having the same CAS number, molecular weight or specification.
Nomifensine acts primarily by inhibiting monoamine neurotransmitter reuptake.
Its pharmacological activity includes:
Research data identify dopamine and norepinephrine uptake as important pharmacological targets of Nomifensine.
Historically, Nomifensine was investigated and marketed as an antidepressant. It has also been used as a research compound for studying monoamine transport and neurotransmitter reuptake.
Current research applications can include:
Analytical literature has described HPLC and spectrophotometric methods for determination of Nomifensine and Nomifensine maleate.
Nomifensine base is described as a crystalline solid, with reported melting point around 179–181°C. Chemical reference sources describe the material as light yellow to yellow crystalline material.
These physical values are useful for chemical identification and reference purposes but should not automatically be represented as formal API release specifications.
Reported solubility for Nomifensine varies according to the solvent and experimental conditions. Reference data report solubility in organic solvents including DMF, DMSO and ethanol, while aqueous solubility depends on pH and formulation conditions.
For CMS purposes, it is preferable to describe solubility qualitatively unless a validated analytical specification is available.
Nomifensine maleate is reported as a crystalline solid with a molecular weight of 354.40 g/mol. Reference data report a melting range around 199–201°C for the maleate salt.
The maleate salt also has different solubility and physical characteristics from the free base and should therefore have its own specification when supplied separately.
A controlled Nomifensine API manufacturing process may involve:
For Nomifensine maleate, an additional salt-formation step using maleic acid may be employed after preparation and purification of the Nomifensine base.
Analytical control of Nomifensine may include:
Published pharmaceutical analytical literature confirms the use of chromatographic and spectrophotometric methods for Nomifensine maleate analysis.
Nomifensine contains a stereogenic center and exists in stereochemically distinct forms. PubChem separately identifies (S)-Nomifensine, confirming the relevance of stereochemical characterization.
Accordingly, if a product is supplied as a racemic Nomifensine material, the specification should clearly identify the stereochemical form. If an enantiomerically enriched material is supplied, enantiomeric purity should be controlled by a validated chiral analytical method.
Nomifensine is not a currently marketed approved antidepressant in the United States. The FDA records the withdrawal of Merital capsules, and PubChem notes withdrawal from the U.S., Canadian and UK markets. The historical withdrawal was associated with serious hemolytic anemia.
Therefore, this API page should avoid implying that Nomifensine is currently approved for routine therapeutic use.
Nomifensine API should be stored in a tightly closed container under controlled conditions, protected from moisture, excessive heat and direct light.
The final storage temperature and packaging requirements should be established from the manufacturer's validated stability data and current specification.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |
| Melting Point | 179–181°C |