Skip to main content
SpringerLink
Log in

Interindividual differences in the binding of antidepressives to plasma proteins: the role of the variants of alpha1-acid glycoprotein

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Alpha1-acid glycoprotein (AAG) is one of the plasma proteins that bind basic drugs, like amitriptyline (AT) and its metabolite nortriptyline (NT). Two types of genetic polymorphism have been described for AAG: polymorphic forms which, on electrophoresis of the native protein, give four patterns with 5, 6, 7 or 8 bands, and the variants which on by electrophoresis of the desialysed protein, give three patterns with 2 bands, FF, FS and SS. In 31 depressive patients, treated daily with 150 mg AT for 3 weeks, free and total plasma AT and NT were determined, as well as the AAG polymorphic forms and variants. There was only a weak negative correlation between the free fractions of AT and NT and total plasma AAG, but free AT and NT were strongly correlated with the S form (but not the F form) of AAG variants. The differences in binding might be the expression of a further genetic factor determining the steady-state plasma levels of tricyclic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Schmid K, Kaufmann H, Isemura S, Bauer F, Emura J, Motoyama T, Ishiguro M, Nanno S (1973) Structure of alpha1-acid glycoprotein. The complete amino acid sequence, multiple amino acid substitution, and homology with the immunoglobulins. Biochemistry 12: 2711–2724

    Google Scholar 

  2. Fournet B, Montreuil J, Strecker G, Dorland L, Haverkamp J, Vliegenthart JFG, Binette JP, Schmid K (1978) Determination of the primary structures of 16 asialo-carbohydrate units derived from human plasma alpha1-acid glycoprotein by 360-MHz 1H NMR spectroscopy and permethylation analysis. Biochemistry 17: 5206–5214

    Google Scholar 

  3. Schmid K, Binette JP, Torika K, Moroz L, Yoshizaki H (1964) The polymorphic forms of alpha1-acid glycoprotein of normal Caucasian individuals. J Clin Invest 43: 2347–2352

    Google Scholar 

  4. Schmid K, Tokita K, Yoshizaki H (1965) The alpha1-acid glycoprotein variants of normal Caucasian and Japanese individuals. J Clin Invest 44: 1394–1401

    Google Scholar 

  5. Borgå O, Azarnoff DL, Forshell GP, Sjöqvist F (1969) Plasma protein binding of tricyclic antidepressants in man. Biochem Pharmacol 18: 2135–2143

    Google Scholar 

  6. Cooper TB, Allen D, Simpson GM (1976) A sensitive method for the determination of amitriptyline in human plasma. Psychopharmacol Commun 2: 105–116

    Google Scholar 

  7. Baumann P, Koeb L, Tinguely D, Rivier L (1982) A method for the analysis of free, total plasma and saliva amitriptyline and nortriptyline by dialysis and gc/ms. Europ J Mass Spectrometr Biochem Med Environ Res 2: 19–26

    Google Scholar 

  8. Tinguely D, Baumann P, Schöpf J (1982) Microprocedure to determine the polymorphic forms of acid alpha1-glycoprotein in plasma. Application to depressive patients treated with amitriptyline. J Chromatogr 229: 319–325

    Google Scholar 

  9. Weimer HE, Mehl JW, Winzler RJ (1950) Studies on the mucoproteins of human plasma. V. Isolation and characterization of a homogeneous mucoprotein. J Biol Chem 185: 561–568

    Google Scholar 

  10. Brinkschulte M, Gaertner HJ, Schied HW, Breyer-Pfaff U (1982) Plasma protein binding of perazine and amitriptyline in psychiatric patients. Eur J Clin Pharmacol 22: 367–373

    Google Scholar 

  11. Piafsky KM, Borgå O (1977) Plasma protein binding of basic drugs. II. Importance of alpha1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22: 545–549

    Google Scholar 

  12. Javaid JI, Hendricks K, Davis JM (1983) High-affinity binding of tricyclic antidepressants to human plasma involves alpha1-acid glycoprotein. Psychopharmacol Bull 19: 655–658

    Google Scholar 

  13. Bertilsson L, Braithwaite R, Tybring G, Garle M, Borgå O (1979) Techniques for plasma protein binding of demethylchlorimipramine. Clin Pharmacol Ther 26: 265–271

    Google Scholar 

  14. Pike E, Skuterud B (1982) Plasma binding variations of amitriptyline and nortriptyline. Clin Pharmacol Ther 32: 228–234

    Google Scholar 

  15. Brinkschulte M, Breyer-Pfaff U (1980) The contribution of alpha1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn-Schmiedebergs Arch Pharmacol 314: 61–66

    Google Scholar 

  16. Kornguth ML, Hutchins LG, Eichelman BS (1981) Binding of psychotropic drugs to isolated alpha1-acid glycoprotein. Biochem Pharmacol 17: 2435–2441

    Google Scholar 

  17. Schley J, Müller-Oerlinghausen B (1983) The binding of chemically different psychotropic drugs to alpha1-acid glycoprotein. Pharmacopsychiatry 16: 82–85

    Google Scholar 

  18. Javaid JI, Hendricks K, Davis JM (1983) Alpha1-acid glycoprotein involvement in high affinity binding of tricyclic antidepressants to human plasma. Biochem Pharmacol 32: 1149–1153

    Google Scholar 

  19. Müller WE, Stillbauer AE (1983) Characterization of a common binding site for basic drugs on human alpha1-acid glycoprotein (Orosomucoid). Naunyn-Schmiedebergs Arch Pharmacol 322: 170–173

    Google Scholar 

  20. Pike E, Skuterud B, Kierulf P, Lunde PKM (1982) Significance of lipoproteins in serum binding variations of amitriptyline, nortriptyline, and quinidine. Clin Pharmacol Ther 32: 599–606

    Google Scholar 

  21. Bickel MH (1975) Binding of chlorpromazine and imipramine to red cells, albumin, lipoporteins and other blood components. J Pharm Pharmacol 27: 733–738

    Google Scholar 

  22. Danon A, Chen Z (1979) Binding of imipramine to plasma proteins: effect of hyperlipoproteinemia. Clin Pharmacol Ther 25: 316–321

    Google Scholar 

  23. Robert L, Migne J, Santoja R, Zini R, Schmid K, Tillement JP (1983) Plasma binding of an alphablocking agent, nicergoline-affinity for serum albumin and native and modified alpha1-acid glycoprotein. Int J Clin Pharmacol Ther Toxicol 21: 271–276

    Google Scholar 

  24. Kute T, Westphal U (1976) Steroid-protein interactions. XXXIV. Chemical modification of alpha1-acid glycoprotein for characterization of the progesterone binding site. Biochim Biophys Acta 420: 195–213

    Google Scholar 

  25. Alexanderson B, Evans DAP, Sjöqvist F (1969) Steadystate plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. Br Med J 4: 764–768

    Google Scholar 

  26. Alexanderson B (1973) Prediction of steady-state plasma levels of nortriptyline from single oral dose kinetics: a study in twins. Eur J Clin Pharmacol 6: 44–53

    Google Scholar 

  27. Alexanderson B, Borgå O (1972) Interindividual differences in plasma protein binding of nortriptyline in man — a twin study. Eur J Clin Pharmacol 4: 196–200

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinique Psychiatrique Universitaire, Hôpital de Cery, Prilly-Lausanne, Switzerland

    D. Tinguely, P. Baumann, M. Conti, M. Jonzier-Perey & J. Schöpf

Authors
  1. D. Tinguely
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Baumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Conti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Jonzier-Perey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Schöpf
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tinguely, D., Baumann, P., Conti, M. et al. Interindividual differences in the binding of antidepressives to plasma proteins: the role of the variants of alpha1-acid glycoprotein. Eur J Clin Pharmacol 27, 661–666 (1985). https://doi.org/10.1007/BF00547045

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00547045

Key words

Search

Navigation