Description
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.
Originator
Alival,Hoechst,W. Germany ,1976
Uses
A novel antidepressant distinguished from existing tricyclic and tetracyclic antidepressants by its bicyclic structure.
Definition
ChEBI: An N-methylated tetrahydroisoquinoline carrying phenyl and amino substituents at positions C-4 and C-8, respectively.
Manufacturing Process
A solution of N-(2-aminobenzyl)-1-phenyl-2-methylaminoethanol-1 was prepared by the reaction of α-bromo-acetophenone and (2nitrobenzyl)methylamine, followed by hydrogenation of the nitro group by means of nickel on diatomaceous earth at room temperature and reduction of the CO group by means of sodium borohydride. The intermediate thus produced was dissolved in 100 ml of methylene chloride and introduced dropwise into 125 ml of sulfuric acid at 10° to 15°C. After a short standing, the reaction mixture was poured onto ice and rendered alkaline by means of a sodium hydroxide solution. By extraction with ether, there was obtained 1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-amino-isoquinoline. The base is reacted with maleic acid to give the maleate; melting point of the maleate 199° to 201°C (from ethanol).
Brand name
Merital (Hoechst-Roussel);Anametrin;Caribium;Hoe 984;Hostalival;Merival;Musettamycin;Neurolene;Nomival;Psicronizer;Psyton.
Therapeutic Function
Psychostimulant
World Health Organization (WHO)
Nomifensine, an antidepressant indicated for the treatment of a
wide range of depressive illness, was introduced in 1976. Subsequently rare cases
of haemolytic anaemia - sometimes fatal - thrombocytopenia, hepatotoxicity and
fever were associated with the use of the drug. Following discussions with
regulatory authorities in the United Kingdom and the Federal Republic of Germany
the major manufacturer withdrew all preparations containing nomifensine
worldwide in January 1986.
Safety Profile
Poison by ingestion andintravenous routes. Human systemic effects by ingestion:diffuse hepatitis, hemorrhage and decrease in the numberof blood platelets (thrombocytopenia). When heated todecomposition it emits toxic fumes of NOx.
