NOMIFENSINE MALEATE

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.

A novel antidepressant distinguished from existing tricyclic and tetracyclic antidepressants by its bicyclic structure.

ChEBI: An N-methylated tetrahydroisoquinoline carrying phenyl and amino substituents at positions C-4 and C-8, respectively.

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.

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.