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Chemical Compound Review

NSC-132087     N,2-dihydroxy-3-methyl- benzamide

Synonyms: NSC132087, AR-1K0328, AKOS000185630, AC1L5SC3, AC1Q5EO0, ...
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Disease relevance of Sparteine

  • Sparteine apparent oral clearance (p < 0.03) and renal clearance (p < 0.001) decreased in patients with renal failure [1].
  • RESULTS: Chronic renal failure was associated with a decrease in sparteine partial metabolic clearance to dehydrosparteine (median of 322 ml/min and range of 62 to 670 ml/min in patients with renal failure versus median of 635 ml/min and range of 77 to 1276 ml/min in normal subjects; p < 0.02) [1].
  • Because the debrisoquine/sparteine mono-oxygenase is a polymorphic enzyme, in which 5-10% of caucasians are deficient in metabolism of various drugs, a genetic difference in human brain metabolism of P450IID1 substrates may possibly lead to differences in drug response and toxicity [2].
  • Steady-state plasma concentrations of paroxetine were studied at five or more paroxetine dose levels (10 to 70 mg/day) in each of 13 extensive metabolizers of sparteine and at three or four dose levels (10 to 40 mg/day) in each of three poor metabolizers of sparteine, all treated for diabetic neuropathy symptoms [3].
  • The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: a meta-analysis [4].

Psychiatry related information on Sparteine


High impact information on Sparteine

  • The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism [6].
  • Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism [6].
  • The liver antigen of liver-kidney microsomal-1 antibodies has been identified as cytochrome P450 db1, a microsomal enzyme catalyzing the oxidative metabolism of more than 20 drugs, including debrisoquine, sparteine and bufuralol [7].
  • The debrisoquine/sparteine-type polymorphism is a clinically important inherited variation of drug metabolism characterized by two phenotypes, the extensive metabolizer and the poor metabolizer (PM) [8].
  • The debrisoquine/sparteine-type polymorphism of drug oxidation presumably is caused by the absence or deficiency of cytochrome P-450 (P-450) isozyme(s) [9].

Chemical compound and disease context of Sparteine

  • METHODS: A single 100 mg oral dose of sparteine and a single 40 mg oral dose of dextromethorphan were administered on two occasions to 12 patients with chronic renal failure (creatinine clearance ranging from 20 to 70 ml/min) and 12 age- and sex-matched healthy subjects [1].

Biological context of Sparteine


Anatomical context of Sparteine

  • Moreover, antibodies raised against rat hepatic enzyme inhibited, in a concentration-dependent manner, sparteine metabolism in canine striatal membranes [2].
  • Microsomes from AH22/pELT cells showed catalytic activity towards metoprolol (alpha-hydroxylation and O-demethylation, 0.17 and 0.78 nmol/mg protein/h, respectively); and towards sparteine (2- and 5-dehydrogenation, 1.82 and 0.59 nmol/mg protein/h, respectively) [14].
  • These results show that sparteine increases insulin release by reducing the K+-permeability of the B-cell membrane [15].
  • Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction [16].
  • In the presence of 10 mM glucose, 0.2 mM sparteine decreased 86Rb+ efflux and increased 45Ca2+ efflux from islet cells [15].

Associations of Sparteine with other chemical compounds


Gene context of Sparteine


Analytical, diagnostic and therapeutic context of Sparteine

  • The analgesic efficacy and kinetics of a single oral dose of 75 mg codeine was investigated in 12 extensive metabolizers and 12 poor metabolizers of sparteine in a double-blind, placebo-controlled crossover study [5].
  • In contrast, five subjects who were poor metabolizers of mephenytoin and extensive metabolizers of sparteine and a control group of 11 subjects who were extensive metabolizers of mephenytoin and sparteine showed no statistically significant difference with regard to these parameters [26].
  • OBJECTIVES: To examine whether the variability of CYP2D6 activity in patients with chronic renal failure can be assessed, particularly among subjects with the extensive metabolizer phenotype, by use of standard in vivo indexes of CYP2D6 activity derived from oral administration of dextromethorphan and sparteine [1].
  • PCR assays were performed to detect this allele and other alleles from a group of subjects exhibiting low rates of sparteine metabolism, i.e. with MRs > 1 [21].
  • The CYP2D6 alleles from two subjects having a high MR, characteristic of slower rates of sparteine metabolism, were cloned in lambda EMBL3 and subjected to sequence analysis [21].


  1. Assessment of individual CYP2D6 activity in extensive metabolizers with renal failure: comparison of sparteine and dextromethorphan. Kévorkian, J.P., Michel, C., Hofmann, U., Jacqz-Aigrain, E., Kroemer, H.K., Peraldi, M.N., Eichelbaum, M., Jaillon, P., Funck-Brentano, C. Clin. Pharmacol. Ther. (1996) [Pubmed]
  2. Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Tyndale, R.F., Sunahara, R., Inaba, T., Kalow, W., Gonzalez, F.J., Niznik, H.B. Mol. Pharmacol. (1991) [Pubmed]
  3. Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: nonlinearity and relation to the sparteine oxidation polymorphism. Sindrup, S.H., Brøsen, K., Gram, L.F. Clin. Pharmacol. Ther. (1992) [Pubmed]
  4. The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: a meta-analysis. Christensen, P.M., Gøtzsche, P.C., Brøsen, K. Pharmacogenetics (1998) [Pubmed]
  5. Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine. Sindrup, S.H., Brøsen, K., Bjerring, P., Arendt-Nielsen, L., Larsen, U., Angelo, H.R., Gram, L.F. Clin. Pharmacol. Ther. (1990) [Pubmed]
  6. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Gaedigk, A., Blum, M., Gaedigk, R., Eichelbaum, M., Meyer, U.A. Am. J. Hum. Genet. (1991) [Pubmed]
  7. Patients with type II autoimmune hepatitis express functionally intact cytochrome P-450 db1 that is inhibited by LKM-1 autoantibodies in vitro but not in vivo. Manns, M., Zanger, U., Gerken, G., Sullivan, K.F., Meyer zum Büschenfelde, K.H., Meyer, U.A., Eichelbaum, M. Hepatology (1990) [Pubmed]
  8. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. Kagimoto, M., Heim, M., Kagimoto, K., Zeugin, T., Meyer, U.A. J. Biol. Chem. (1990) [Pubmed]
  9. Debrisoquine/sparteine-type polymorphism of drug oxidation. Purification and characterization of two functionally different human liver cytochrome P-450 isozymes involved in impaired hydroxylation of the prototype substrate bufuralol. Gut, J., Catin, T., Dayer, P., Kronbach, T., Zanger, U., Meyer, U.A. J. Biol. Chem. (1986) [Pubmed]
  10. Characterization of a human liver cytochrome P-450 involved in the oxidation of debrisoquine and other drugs by using antibodies raised to the analogous rat enzyme. Distlerath, L.M., Guengerich, F.P. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  11. The genetic polymorphism of debrisoquine/sparteine metabolism--clinical aspects. Eichelbaum, M., Gross, A.S. Pharmacol. Ther. (1990) [Pubmed]
  12. The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide. Mikus, G., Gross, A.S., Beckmann, J., Hertrampf, R., Gundert-Remy, U., Eichelbaum, M. Clin. Pharmacol. Ther. (1989) [Pubmed]
  13. Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Nielsen, K.K., Brøsen, K., Hansen, M.G., Gram, L.F. Clin. Pharmacol. Ther. (1994) [Pubmed]
  14. Catalytic activities of human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) expressed in yeast. Ellis, S.W., Ching, M.S., Watson, P.F., Henderson, C.J., Simula, A.P., Lennard, M.S., Tucker, G.T., Woods, H.F. Biochem. Pharmacol. (1992) [Pubmed]
  15. Sparteine increases insulin release by decreasing the K+ permeability of the B-cell membrane. Paolisso, G., Nenquin, M., Schmeer, W., Mathot, F., Meissner, H.P., Henquin, J.C. Biochem. Pharmacol. (1985) [Pubmed]
  16. Aminopyridines and sparteine as inhibitors of membrane potassium conductance: effects on Myxicola giant axons and the lobster neuromuscular junction. Schauf, C.L., Colton, C.A., Colton, J.S., Davis, F.A. J. Pharmacol. Exp. Ther. (1976) [Pubmed]
  17. Sparteine oxidation by the human liver: absence of inhibition by mephenytoin. Jurima, M., Inaba, T., Kalow, W. Clin. Pharmacol. Ther. (1984) [Pubmed]
  18. The relationship between paroxetine and the sparteine oxidation polymorphism. Sindrup, S.H., Brøsen, K., Gram, L.F., Hallas, J., Skjelbo, E., Allen, A., Allen, G.D., Cooper, S.M., Mellows, G., Tasker, T.C. Clin. Pharmacol. Ther. (1992) [Pubmed]
  19. Evidence for a dissociation in the control of sparteine, debrisoquine and metoprolol metabolism in Nigerians. Lennard, M.S., Iyun, A.O., Jackson, P.R., Tucker, G.T., Woods, H.F. Pharmacogenetics (1992) [Pubmed]
  20. Influence of enzyme induction and inhibition on the oxidation of nifedipine, sparteine, mephenytoin and antipyrine in humans as assessed by a "cocktail" study design. Schellens, J.H., van der Wart, J.H., Brugman, M., Breimer, D.D. J. Pharmacol. Exp. Ther. (1989) [Pubmed]
  21. Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism. Yokota, H., Tamura, S., Furuya, H., Kimura, S., Watanabe, M., Kanazawa, I., Kondo, I., Gonzalez, F.J. Pharmacogenetics (1993) [Pubmed]
  22. 4-Hydroxylation of debrisoquine by human CYP1A1 and its inhibition by quinidine and quinine. Granvil, C.P., Krausz, K.W., Gelboin, H.V., Idle, J.R., Gonzalez, F.J. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  23. Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and CYP2A6 genes in Japanese. Yokoi, T., Kamataki, T. Pharm. Res. (1998) [Pubmed]
  24. Mechanism of cytochrome P450 2D6-catalyzed sparteine metabolism in humans. Ebner, T., Meese, C.O., Eichelbaum, M. Mol. Pharmacol. (1995) [Pubmed]
  25. Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients. Liou, Y.J., Wang, Y.C., Bai, Y.M., Lin, C.C., Yu, S.C., Liao, D.L., Lin, M.W., Chen, J.Y., Lai, I.C. Neuropsychobiology (2004) [Pubmed]
  26. The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Skjelbo, E., Brøsen, K., Hallas, J., Gram, L.F. Clin. Pharmacol. Ther. (1991) [Pubmed]
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