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Chemical Compound Review

Lopac-N-1530     (4S)-2-methyl-4-phenyl-3,4- dihydro-1H...

Synonyms: CHEMBL51697, CHEBI:180847, LS-86010, ZINC19796033, BRN 6064060, ...
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Disease relevance of BRN 6064060


Psychiatry related information on BRN 6064060


High impact information on BRN 6064060

  • To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens [10].
  • Additionally, 3H-dopamine release occurred in vitro through a Ca(2+)-dependent mechanism, as well as through reverse function of a nomifensine-sensitive dopamine transporter [11].
  • Pharmacological protection of dopaminergic nerve terminals with nomifensine abolished MPTP-mediated phosphorylation and translocation of STAT3 and prevented induction of astrogliosis [12].
  • 18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively [13].
  • Treatment of bulimia with nomifensine [14].

Chemical compound and disease context of BRN 6064060

  • After addition of tetrodotoxin (40 microM) to the perfusion fluid or pretreatment with nomifensine (100 mg/kg, i.p.), exposure to hypoxia no longer increased the dopamine levels [15].
  • However, 100 microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine [16].
  • In CNic cultures, basal DA levels were also elevated (approximately 9x control), similar to that in CHox cultures; however, although acute hypoxia had a stimulatory effect on DA release (approximately 2x basal), nicotine, nomifensine, and high K+ were ineffective [17].
  • Hypothermia induced by a high dose of apomorphine (16 mg/kg) is not antagonized by neuroleptics, but is strongly antagonized by antidepressants (imipramine-like drugs, amineptine, amoxapine, nomifensine, viloxazine) and potential antidepressants (beta-adrenergic stimulants) [18].
  • In the treatment of Parkinsonism, nomifensine may be considered as an alternative to amantadine or anticholinergics, especially where depression is an added feature [19].

Biological context of BRN 6064060

  • The pharmacokinetics of nomifensine were studied after single oral and intravenous doses [20].
  • The AUC of free nomifensine decreased substantially (from 0.78 to 0.32 hr X mumol/L) and the elimination t1/2 was shortened (from 4.39 to 2.11 hours) after a 2-week dosing period [20].
  • Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin [21].
  • Kinetics and metabolism of nomifensine [22].
  • Nomifensine, a DA reuptake inhibitor, rescued nearly 60-70% of the cells from DA- and DA plus KCN-induced apoptosis, suggesting that DA toxicity is in part mediated intracellularly [23].

Anatomical context of BRN 6064060


Associations of BRN 6064060 with other chemical compounds

  • Evaluation of individual patients showed that only one patient had a normal PRL response to either Nom or Dom, while the TSH response to the latter returned to normal in five of seven patients [27].
  • The release evoked by 5-HT in the presence of 10 microM nomifensine (an antagonist of the DA transporter) was less than in its absence, but the difference between weaver and +/+ striatum remained [28].
  • Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR-12909 (10-1,000 microM) or nomifensine (10-1,000 microM) dose-dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA [29].
  • The uptake of [3H]5-hydroxytryptamine ([3H]5-HT) into synaptosomal preparations of substantia nigra was abolished by fluoxetine and reduced by desipramine, but was unaffected by nomifensine [30].
  • In the bioavailability study, 24 men received single oral 50 mg doses of nomifensine maleate in a capsule or as an aqueous solution [31].

Gene context of BRN 6064060

  • Thyrotropin-releasing hormone, nomifensine, and domperidone produced standard PRL responses in normoprolactinemic patients but not in hyperprolactinemic patients [32].
  • Since basal DA levels were low, the experiments were performed under local infusion of the reuptake inhibitor nomifensine (5 mumol/l), which increased extracellular DA levels 5-fold around the probe, but did not affect the occurrence of the nocturnal PRL surge on day 7-8 of PSP [33].
  • The following serotoninergic drugs were perfused in the absence or presence of nomifensine (5 microM) or tetrodotoxin (TTX; 2 microM): clomipramine (10, 500 and 1,000 microM), a selective 5-HT reuptake inhibitor; 8-OH-DPAT (50 and 500 microM), a 5-HT1A receptor agonist; and alpha-methyl-5-HT (1, 5 and 50 microM), a 5-HT2 receptor agonist [34].
  • Nomifensine administration had no appreciable effect on the TRH-induced release of TSH and prolactin [35].
  • Some drugs elicit antibodies that react at specific sites on the cell membrane independently of drug (eg, nomifensine and the Rh antigens (E) or quinidine and platelet GPV) [36].

Analytical, diagnostic and therapeutic context of BRN 6064060


  1. The role of metabolite-specific antibodies in nomifensine-dependent immune hemolytic anemia. Salama, A., Mueller-Eckhardt, C. N. Engl. J. Med. (1985) [Pubmed]
  2. Nomifensine-induced allergic reactions. Miescher, P.A. Lancet (1985) [Pubmed]
  3. Fatal necrotising vasculitis associated with nomifensine. Schönhöfer, P.S., Gröticke, J. Lancet (1985) [Pubmed]
  4. Nomifensine, acute hemolytic anemia, and renal failure. Bloomfield, R.J., Wilson, I.J. Ann. Intern. Med. (1986) [Pubmed]
  5. The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents. Tucker, J.C., File, S.E. Neuroscience and biobehavioral reviews. (1986) [Pubmed]
  6. Nomifensine exacerbates narcolepsy. Sandyk, R., Gillman, M.A. Neurology (1985) [Pubmed]
  7. Efficacy of nomifensine in different depressive syndromes. Overall, J.E. The Journal of clinical psychiatry. (1984) [Pubmed]
  8. Pharmacodynamics of nomifensine: a review of studies in healthy subjects. Siegfried, K., Taeuber, K. The Journal of clinical psychiatry. (1984) [Pubmed]
  9. Multicenter double-blind comparison of nomifensine and imipramine for efficacy and safety in depressed outpatients. Bremner, J.D., Abrahams, L.M., Crupie, J.E., McCawley, A., Proctor, R.C., Sathananthan, G.L. The Journal of clinical psychiatry. (1984) [Pubmed]
  10. On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia. Salama, A., Mueller-Eckhardt, C. Blood (1987) [Pubmed]
  11. Photomechanical movements of cultured embryonic photoreceptors: regulation by exogenous neuromodulators and by a regulable source of endogenous dopamine. Stenkamp, D.L., Iuvone, P.M., Adler, R. J. Neurosci. (1994) [Pubmed]
  12. Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? Sriram, K., Benkovic, S.A., Hebert, M.A., Miller, D.B., O'Callaghan, J.P. J. Biol. Chem. (2004) [Pubmed]
  13. The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. Brooks, D.J., Salmon, E.P., Mathias, C.J., Quinn, N., Leenders, K.L., Bannister, R., Marsden, C.D., Frackowiak, R.S. Brain (1990) [Pubmed]
  14. Treatment of bulimia with nomifensine. Pope, H.G., Herridge, P.L., Hudson, J.I., Fontaine, R., Yurgelun-Todd, D. The American journal of psychiatry. (1986) [Pubmed]
  15. Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain microdialysis. Akiyama, Y., Koshimura, K., Ohue, T., Lee, K., Miwa, S., Yamagata, S., Kikuchi, H. J. Neurochem. (1991) [Pubmed]
  16. Monoamine transporter inhibitors and norepinephrine reduce dopamine-dependent iron toxicity in cells derived from the substantia nigra. Paris, I., Martinez-Alvarado, P., Perez-Pastene, C., Vieira, M.N., Olea-Azar, C., Raisman-Vozari, R., Cardenas, S., Graumann, R., Caviedes, P., Segura-Aguilar, J. J. Neurochem. (2005) [Pubmed]
  17. Role of acetylcholine receptors and dopamine transporter in regulation of extracellular dopamine in rat carotid body cultures grown in chronic hypoxia or nicotine. Jackson, A., Nurse, C.A. J. Neurochem. (1998) [Pubmed]
  18. Antagonism of hypothermia and behavioral response to apomorphine: a simple, rapid and discriminating test for screening antidepressants and neuroleptics. Puech, A.J., Chermat, R., Poncelet, M., Doaré, L., Simon, P. Psychopharmacology (Berl.) (1981) [Pubmed]
  19. Nomifensine: effect in Parkinsonian patients not receiving levodopa. Park, D.M., Findley, L.J., Hanks, G., Sandler, M. J. Neurol. Neurosurg. Psychiatr. (1981) [Pubmed]
  20. Disposition of nomifensine after acute and prolonged dosing. Lindberg, R.L., Syvälahti, E.K., Pihlajamäki, K.K. Clin. Pharmacol. Ther. (1986) [Pubmed]
  21. Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers. Scheinin, M., Lindberg, R., Syvälahti, E., Hietala, J., Pihlajamäki, K., Scheinin, H. Clin. Pharmacol. Ther. (1987) [Pubmed]
  22. Kinetics and metabolism of nomifensine. Heptner, W., Hornke, I., Uihlein, M. The Journal of clinical psychiatry. (1984) [Pubmed]
  23. Dopamine-induced apoptosis is mediated by oxidative stress and Is enhanced by cyanide in differentiated PC12 cells. Jones, D.C., Gunasekar, P.G., Borowitz, J.L., Isom, G.E. J. Neurochem. (2000) [Pubmed]
  24. Chronic inhibition of the high-affinity dopamine uptake system increases oxidative damage to proteins in the aged rat substantia nigra. Romero-Ramos, M., Rodríguez-Gómez, J.A., Venero, J.L., Cano, J., Machado, A. Free Radic. Biol. Med. (1997) [Pubmed]
  25. Effects of D-2 antagonists on frequency-dependent stimulated dopamine overflow in nucleus accumbens and caudate-putamen. May, L.J., Wightman, R.M. J. Neurochem. (1989) [Pubmed]
  26. In vivo assessment of dopamine and norepinephrine release in rat neocortex: gas chromatography-mass spectrometry measurement of 3-methoxytyramine and normetanephrine. Wood, P.L., Kim, H.S., Altar, C.A. J. Neurochem. (1987) [Pubmed]
  27. Defective regulation of prolactin secretion after successful removal of prolactinomas. Camanni, F., Ghigo, E., Ciccarelli, E., Massara, F., Campagnoli, C., Molinatti, G., Müller, E.E. J. Clin. Endocrinol. Metab. (1983) [Pubmed]
  28. Dopamine transporter-dependent and -independent endogenous dopamine release from weaver mouse striatum in vitro. Richter, J.A., Bare, D.J., Yu, H., Ghetti, B., Simon, J.R. J. Neurochem. (1995) [Pubmed]
  29. Feedback control of mesolimbic somatodendritic dopamine release in rat brain. Rahman, S., McBride, W.J. J. Neurochem. (2000) [Pubmed]
  30. Evidence that [3H]dopamine is taken up and released from nondopaminergic nerve terminals in the rat substantia nigra in vitro. Kelly, E., Jenner, P., Marsden, C.D. J. Neurochem. (1985) [Pubmed]
  31. The pharmacokinetics and bioavailability of nomifensine maleate in healthy men. Lassman, H.B., Puri, S.K., Ho, I., Sabo, R., Rosenkilde, H.C. The Journal of clinical psychiatry. (1984) [Pubmed]
  32. Prolactin secretion after surgery or bromocriptine treatment of prolactinoma. De Leo, V., Petraglia, F., Sardelli, S., Danero, S., Genazzani, A.R., D'Antona, N. Obstetrics and gynecology. (1987) [Pubmed]
  33. Semicircadian rhythm of dopamine release in the mediobasal hypothalamus in awake rats during pseudopregnancy: evidence that a thyrotropin-releasing hormone analogue stimulates dopamine release and thereby inhibits prolactin secretion. Timmerman, W., Poelman, R.T., Westerink, B.H., Schuiling, G.A. Neuroendocrinology (1995) [Pubmed]
  34. Influence of serotoninergic drugs on in vivo dopamine extracellular output in rat striatum. Santiago, M., Matarredona, E.R., Machado, A., Cano, J. J. Neurosci. Res. (1998) [Pubmed]
  35. Inhibition of prolactin secretion by nomifensine in man. Masala, A., Alagna, S., Devilla, L., Delitala, G., Rovasio, P.P. Clin. Endocrinol. (Oxf) (1980) [Pubmed]
  36. Specificity of drug-induced immune cytopenias. Christie, D.J. Transfusion medicine reviews. (1993) [Pubmed]
  37. Intravenous self-administration of nomifensine in rats: implications for abuse potential in humans. Spyraki, C., Fibiger, H.C. Science (1981) [Pubmed]
  38. Characterization of dopamine release in the substantia nigra by in vivo microdialysis in freely moving rats. Robertson, G.S., Damsma, G., Fibiger, H.C. J. Neurosci. (1991) [Pubmed]
  39. Effects of nomifensine on growth hormone and prolactin secretion in normal subjects and in pathological hyperprolactinemia. Dallabonzana, D., Spelta, B., Botalla, L., Oppizzi, G., Silvestrini, F., Chiodini, P.G., Liuzzi, A. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  40. Nomifensine: diagnostic test in hyperprolactinemic states. Müller, E.E., Genazzani, A.R., Murru, S. J. Clin. Endocrinol. Metab. (1978) [Pubmed]
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