Skip to main content
Log in

Characterization of a common binding site for basic drugs on human α2-acid glycoprotein (orosomucoid)

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The interaction of chlorpromazine, dl-propranolol, and imipramine with isolated α1-acid glycoprotein is characterized by relatively high association constants and only one binding site per protein molecule. The mutual displacement between the three drugs indicates that all three compounds are bound to the same binding site. Several other basic drugs from different pharmacological and chemical classes also displace chlorpromazine, dl-propranolol, and imipramine with potencies, one would predict from their association constants or from the degree of their plasma binding in humans. It is concluded that displacement phenomena like those observed in this study in vitro are likely to occur also in vivo.

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

Access this article

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

  • Borga O, Azarnoff DL, Plym Forshell G, Sjöqvist F (1969) Plasma protein binding of tricyclic antidepressants in man. Biochem Pharmacol 18:2135–2143

    Google Scholar 

  • Brinkschulte M, Breyer-Pfaff U (1980) The contribution of α1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn-Schmiedeberg's Arch Pharmacol 314:61–66

    Google Scholar 

  • Brooks MH, Malloy JP, Bartelloni PJ, Sheehy TW, Barry KG (1969) Quinine, pyrimethamine, and sulphortodimethoxine: clinical response, plasma levels, and urinary excretion during the initial attack of naturally acquired falciparum malaria. Clin Pharmacol Ther 10:85–91

    Google Scholar 

  • De Leve LD, Piafsky KM (1981) Clinical significance of plasma binding of basic drugs. TIPS 283–284

  • El-Gamal S, Wollert U, Müller WE (1982) Optical studies on the specific interaction of dipyridamole with α1-acid glycoprotein. J Pharm Pharmacol 34:152–157

    Google Scholar 

  • El-Gamal S, Wollert U, Müller WE (1983) The binding of several phenothiazine neuroleptics to a common binding site of α1-acid glycoprotein (orosomucoid). J Pharm Sci (in press)

  • Fehske KJ, Müller WE, Wollert U (1981) The location of drug binding sites in human serum albumin. Biochem Pharmacol 30:687–692

    Google Scholar 

  • Fremdstad D, Bergerud K, Haffner JFW, Lunde PKM (1976) Increased plasma binding of quinidine after surgery. A preliminary report. Eur J Clin Pharmacol 10:441–444

    Google Scholar 

  • Ganguly M, Westphal U (1968) Steroid-protein interactions. XVII. Influence of solvent environment on interaction between human α1-acid glycoprotein and progesterone. J Biol Chem 243:6130–6139

    Google Scholar 

  • Glasson S, Zini R, D'Athis P, Tillement JP, Boissier JR (1980) The distribution of bound propranolol between the different human serum proteins. Mol Pharmacol 17:187–191

    Google Scholar 

  • Jähnchen E, Bechtold H, Kasper W, Kersting F, Just H, Meinertz T (1979) Lorcainide. I. Saturable presystemic elimination. Clin Pharmacol Ther 26:187–195

    Google Scholar 

  • Kerkay J, Westphal U (1969) Steroid-protein interactions. XXI. Metal ion inhibition of association between progesterone and 172-5 glycoprotein. Arch Biochem Biophys 129:480–489

    Google Scholar 

  • Kopitar Z, Weisenberger H (1971) Spezifische Bindung von Dipyridamol an ein menschliches Serumprotein. Arzneimittelforschung 21: 859–862

    Google Scholar 

  • Kornguth ML, Hutchins LG, Eichelman BS (1981) Binding of psychotropic drugs to isolated 172-6 glycoprotein. Biochem Pharmacol 30:2435–2441

    Google Scholar 

  • Kragh-Hansen U (1981) Molecular aspects of ligand binding to serum albumin. Pharmacol Rev 33:17–53

    Google Scholar 

  • Kute T, Westphal U (1971) Chemical modification of α1-acid glycoprotein for characterization of the progesterone binding site. Biochem Biophys Acta 420:195–213

    Google Scholar 

  • Lima JJ, Boudoulas H, Blanford M (1981) Concentration-dependence of disopyramide binding to plasma protein and its influence on kinetics and dynamics. J Pharmacol Exp Ther 219:741–747

    Google Scholar 

  • Müller WE, Wollert U (1979) Human serum albumin as a “silent receptor” for drugs and endogenous substances. Pharmacology 19:59–67

    Google Scholar 

  • Piafsky KM (1980) Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet 5:246–262

    Google Scholar 

  • Piafsky KM, Knoppert D (1978) Binding of local anesthetics to α1-acid glycoprotein. Clin Res 26:836A

    Google Scholar 

  • Piafsky KM, Borga O, Odar-Cederlöf I, Johansson C, Sjöqvist F (1978) Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α1-acid glycoprotein. N Engl J Med 299:1435–1438

    Google Scholar 

  • Romach MK, Piafsky KM, Abel JG, Khouw V, Sellers EM (1981) Methadone binding to orosomucoid (α1-acid glycoprotein): determinant of free fraction in plasma. Clin Pharmacol Ther 29: 211–217

    Google Scholar 

  • Routledge PA, Shand DG, Barchowsky A, Wagner G, Stargel WW (1981) Relationship between α1-acid glycoprotein and lidocaine disposition in myocardial infarction. Clin Pharmacol Ther 30: 154–157

    Google Scholar 

  • Sager G, Nilsen OG, Jacobsen S (1979) Variable binding of propranolol in human serum. Biochem Pharmacol 28:905–911

    Google Scholar 

  • Schley J, Nündel M, Siegert M, Riedel E, Müller-Oerlinghausen B (1980) High affinity binding of perazine and desmethylperazine to human α1-acid glycoprotein. Pharmacopsychiat 13:144–145

    Google Scholar 

  • Tucker GT, Mather LE (1979) Clinical pharmacokinetics of local anaesthetics. Clin Pharmacokin 4:241–278

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by a grant of the Deutsche Forschungsgemeinschaft

Rights and permissions

Reprints and permissions

About this article

Cite this article

Müller, W.E., Stillbauer, A.E. Characterization of a common binding site for basic drugs on human α2-acid glycoprotein (orosomucoid). Naunyn-Schmiedeberg's Arch. Pharmacol. 322, 170–173 (1983). https://doi.org/10.1007/BF00512392

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00512392

Key words

Navigation