24526-64-5 Usage
Description
NOMIFENSINE MALEATE is a bicyclic antidepressant that is structurally distinct from tricyclic and tetracyclic antidepressants. It functions as an inhibitor of norepinephrine (NE) and dopamine (DA) reuptake, with additional inhibition of serotonin (5-HT) reuptake. NOMIFENSINE MALEATE is characterized by its N-methylated tetrahydroisoquinoline structure with phenyl and amino substituents at positions C-4 and C-8, respectively. It is known for its selectivity in inhibiting DA, NE, and 5-HT uptake over binding to various receptors such as dopamine D2, α1-adrenergic, 5-HT2, and muscarinic receptors.
Uses
Used in Pharmaceutical Industry:
NOMIFENSINE MALEATE is used as an antidepressant for treating depressive disorders. It is particularly effective due to its unique bicyclic structure, which distinguishes it from existing tricyclic and tetracyclic antidepressants. The compound's ability to inhibit the reuptake of NE, DA, and 5-HT contributes to its antidepressant activity, making it a valuable option for patients suffering from depression.
Additionally, NOMIFENSINE MALEATE has demonstrated potential in modulating various signaling pathways related to depression, which could further enhance its therapeutic effects. Its selectivity for inhibiting NE and DA uptake over binding to other receptors may also contribute to a more favorable side effect profile compared to other antidepressants.
Originator
Alival,Hoechst,W. Germany ,1976
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).
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.
Check Digit Verification of cas no
The CAS Registry Mumber 24526-64-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,4,5,2 and 6 respectively; the second part has 2 digits, 6 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 24526-64:
(7*2)+(6*4)+(5*5)+(4*2)+(3*6)+(2*6)+(1*4)=105
105 % 10 = 5
So 24526-64-5 is a valid CAS Registry Number.
InChI:InChI=1/C16H18N2/c1-18-10-14(12-6-3-2-4-7-12)13-8-5-9-16(17)15(13)11-18/h2-9,14H,10-11,17H2,1H3
24526-64-5Relevant articles and documents
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors
Pechulis, Anthony D.,Beck, James P.,Curry, Matt A.,Wolf, Mark A.,Harms, Arthur E.,Xi, Ning,Opalka, Chet,Sweet, Mark P.,Yang, Zhicai,Vellekoop, A. Samuel,Klos, Andrew M.,Crocker, Peter J.,Hassler, Carla,Laws, Mia,Kitchen, Douglas B.,Smith, Mark A.,Olson, Richard E.,Liu, Shuang,Molino, Bruce F.
, p. 7219 - 7222 (2013/01/15)
Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.
An Improved Synthesis of 8-Amino-2-methyl-4-phenyl-1,2,3,4-Tetrahydroisoquinoline
Ivanov, T. B.,Mondeshka, Diana M.,Angelova, Ivanka G.
, p. 731 - 735 (2007/10/02)
The regioselectivity of the reaction of 2-nitrobenzylmethylamine (1) and styrenoxide (2) leading to a mixture of the isomeric aminoalcohols 3a and 3b has been studied.The course of the reaction strongly depends on the type of the solvent used as reaction medium.The highest selectivity (3a:3b=9:1) was achieved with a combination of polar aprotic and protic solvents (DMFA and ethanol). 1H n.m.r. spectroscopy was used for identification of the isomers as well as for the determination of their ratio in the crude reaction mixtures.The isomer ratio remains unaffected during catalytic reduction (Ra-Ni) of 3a/3b to a mixture of the correspondi ng aminoalcohols 4a and 4b.Pure 3a, 4a and 4b were independently synthesized for comparison.Cyclodehydration of crude 4a/4b mixtures gives 5 in a very good yield.
Analytical chemistry of psychotropic drugs: nomifensin
Eiden,Schmiz
, p. 611 - 614 (2007/10/05)
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