Nomifensine
linamiphen · Nomifensin · Nomifenison · Nomifensine, 10 mM in DMSO · NOMIFENSINE MALEATE USP/EP/BP · Dopamine Receptor,Inhibitor,Nomifensine,inhibit · 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinamin · 2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-amine
Identifikatoren & physikalische Daten
| CAS No. | 24526-64-5 |
|---|---|
| Summenformel | C16H18N2 |
| Durchschnittliche Molmasse | 238,33 g/mol |
| Monoisotopische Masse | 238,14699858 g/mol |
| SMILES | CN1Cc2c(N)cccc2C(c2ccccc2)C1 |
| InChIKey | XXPANQJNYNUNES-UHFFFAOYSA-N |
| PubChem CID | 4528 |
| ChEMBL | CHEMBL273575 |
| ChEBI | CHEBI:116225 |
| EC No. | 963-274-9 |
| DTXSID | DTXSID0023377 |
Chemische & physikalische Eigenschaften
| XLogP | 2,6 |
|---|---|
| Polarare Oberfläche (TPSA) | 29,3 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 1 |
| Schwere Atome | 18 |
| Formalladung | 0 |
| Komplexität | 272 |
| Human Drugs | Pharmaceuticals |
| Decomposition | When heated decomposition it emits toxic fumes of NOx. |
| Schmelzpunkt | 179-181 °C179-181° |
| Collision Cross Section | 155.8 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: APCI+Dataset: TOXCASTSource Identifier: DTXSID0023377]154.65 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Siedepunkt | 370.93°C (rough estimate) |
| Dichte | 0.9597 (rough estimate) |
| Brechungsindex | 1.5000 (estimate) |
| Lagerbedingungen | 2-8°C(protect from light) |
| Löslichkeit | DMF: 25 mg/mlDMSO: 25 mg/mlEthanol: 10 mg/mlPBS (pH 7.2): Partially soluble |
| Aggregatzustand | A crystalline solid |
| pKa (Säurekonstante) | 7.85±0.40(Predicted) |
| Farbe | Light yellow to yellow |
| EPA chemische Informationen | Nomifensine (24526-64-5) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P354+P338, P317, P319, P321, P330, P332+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory. |
|---|---|
| FDA-Anforderungen | Drug products withdrawn or removed from the market for reasons of safety or effectiveness. The following drug product was withdrawn or removed from the market because such drug product or component of such drug product was found to be unsafe or not effective. The following drug product may not be compounded under the exemptions provided by section 503A(a) of the Federal Food, Drug, and Cosmetic Act: normifensine maleate. /Nomifensine maleate/ |
| Hazard Classes and Categories | Acute Tox. 3 (100%) |
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Wechselwirkungen | Six epileptic patients (aged 21-28 yr) on either phenytoin and phenobarbital (phenobarbitone) or phenytoin and carbamazepine, and 6 controls (aged 21-25 yr), were given single oral doses of 30 mg mianserin and 100 mg of nomifensine, at least one month apart, to determine if treatment with anticonvulsants would influence the pharmacokinetics of mianserin and nomifensine. The results showed that plasma levels of mianserin and nomifensine were significantly reduced in epileptic patients treated with anticonvulsants. |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ In two large series of cases (193 total) of nomifensine overdose (63 with nomifensine alone) reported to regional poison centers the most common symptoms noted included drowsiness, sinus tachycardia, and tremor. Once case each of coma and ventricular ectopy have been reported. Central nervous system toxicity (excitement, coma, and other) has been observed when nomifensine is ingested with other substances such as benzodiazepines and /or alcohol. There have been no cases of seizures and no deaths associated with nomifensine overdosage alone./CASE REPORTS/ Nomifensine was introduced as an effective antidepressant drug with few side effects. However, among our patients we have seen 2 typical cases of drug fever due to nomifensine. 2-4 weeks after start of nomifensine treatment, 75-150 mg/day, for recurrent endogenous depressions the patients developed shiverings and fever. Nomifensine was withdrawn and both became afebrile within 1 day. A provocation test with 50 mg nomifensine p.o. again resulted in shiverings and fever within 6-8 hr 1 of the patients was allergic to other drugs and suffered from asthma. During the acute episode of illness the serum concentration of alanine aminotransferase was elevated and it normalized after stopping the treatment. A liver biopsy at that time showed liver cell necrosis, and a moderate grade of steatosis and fibrosis was also present. The results indicate that nomifensine may cause drug fever. It is possible that patients with allergy and/or liver diseases in particular may be susceptible to drug fever due to nomifensine. |
Anwendungen & Verwendung
Beschreibung
Nomifensine is an inhibitor of norepinephrine (NE) and dopamine (DA) reuptake. It inhibits uptake of NE, DA, and serotonin (5-HT) in rat brain synaptosomes with IC50 values of 6.6, 48, and 830 nM, respectively. It is selective for DA, NE, and 5-HT uptake inhibition over binding to dopamine D2, α1- adrenergic-, 5-HT2, and muscarinic receptors (IC50s = 43,000, 1,200, 3,800, and >13,000 nM, respectively, in rat brain membranes). Nomifensine is selective for inhibition of NE over DA uptake in vivo with minimal inhibitory doses of 28 and less than 57 μmol/kg, respectively. It decreases the time Wistar Kyoto, but not Sprague-Dawley, rats spend immobile in the forced swim test but also increases locomotor activity in the open field test in Wistar Kyoto and Sprague-Dawley rats when administered at a chronic dose of 10 mg/kg.
Verwenden
A novel antidepressant distinguished from existing tricyclic and tetracyclic antidepressants by its bicyclic structure.