Skip to main content
SpringerLink
Log in

β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The inhibitory action of a range ofβ-carbolines on human and rat monoamine oxidase (MAO) A and B has been studied. Concentrations of 5-hydroxytryptamine and phenylethylamine, approximately at their Km values, were used as substrates for MAO A and B respectively. A wide variation in selectivity was found, with harmaline being 10,000 times more potent an inhibitor of A than B whereas, using tetrahydro-β-carboline and harmane, the difference was nearer to ten-fold. Of the carbolines which have been found endogenously, tetrahydro-β-carboline, 6-methoxytetrahydro-β-carboline and harmane are all sufficiently potent inhibitors of human MAO A, with I50 values of 5×10−6, 10−6, 5×10−7M respectively, for this property to be of possible physiological significance. Harmane, with an I50 of 5×10−6M, might also play a role as an inhibitor of MAO B.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Airaksinen, M. M., Kari, I.:β-Carbolines, psychoactive compounds in the mammalian body. Med. Biol.59, 21–23 (1981).

    PubMed  Google Scholar 

  • Barker, S. A., Harrison, R. E. W., Monti, J. A., Brown, G. B., Christian, S. T.: Identification and quantification of 1, 2, 3, 4-tetrahydro-β-carboline, 2-methyl-1, 2, 3, 4-tetrahydro-β-carboline, and 6-methoxy-1, 2, 3, 4-tetrahydro-β-carboline asin vivo constituents of rat brain and adrenal gland. Biochem. Pharmac.30, 9–17 (1981).

    Google Scholar 

  • Bidder, T. G., Shoemaker, D. W., Boettger, H. G., Evans, M., Cummins, J. T.: Harman in human platelets. Life Sci.25, 157–164 (1979).

    PubMed  Google Scholar 

  • Braestrup, C., Nielsen, M., Olsen, C. E.: Urinary and brainβ-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Nat. Acad. Sci. U.S.A.77, 2288–2292 (1980).

    Google Scholar 

  • Buckholtz, N. S., Boggan, W. O.: Monoamine oxidase inhibition in brain and liver produced byβ-carbolines: structure-activity relationships and substrate specificity. Biochem. Pharmac.26, 1991–1996 (1977).

    Google Scholar 

  • Donnelly, C. H., Murphy, D. L.: Substrate- and inhibitor-related characteristics of human platelet monoamine oxidase. Biochem. Pharmac.26, 853–858 (1977).

    Google Scholar 

  • Edwards, D. J., Chang, S. S.: Multiple forms of monoamine oxidase in rabbit platelets. Life Sci.17, 1127–1134 (1975).

    PubMed  Google Scholar 

  • Egashira, T.: Studies on monoamine oxidase. XVII. Enzymic properties of placental monoamine oxidase. Jap. J. Pharmac.26, 493–500 (1976).

    Google Scholar 

  • Elsworth, J., Glover, V., Sandler, M.:tele-Methylhistamine is a specific MAO B substrate in man. Psychopharmacology69, 287–290 (1980).

    PubMed  Google Scholar 

  • Glover, V., Bhattacharya, S. K., Sandler, M., File, S. E.: Benzodiazepines reduce stress-augmented increase in rat urine monoamine oxidase inhibitor. Nature (London)292, 347–349 (1981a).

    Google Scholar 

  • Glover, V., Peatfield, R., Zammit-Pace, R., Littlewood, J., Gawel, M., Rose, F. C., Sandler, M.: Platelet monoamine oxidase activity and headache. J. Neurol. Neurosurg. Psychiat.44, 786–790 (1981 b).

    PubMed  Google Scholar 

  • Glover, V., Reveley, M. A., Sandler, M.: A monoamine oxidase inhibitor in human urine. Biochem. Pharmac.29, 467–470 (1980).

    Google Scholar 

  • Ho, B. T., McIsaac, W. M., Walker, K. E.: Inhibitors of monoamine oxidase II. Syntheses of some N-2(9)-substituted tetrahydro-β-carbolines and evaluation of their inhibitory activities. J. Pharm. Sci.57, 1364–1369 (1968 a).

    PubMed  Google Scholar 

  • Ho, B. T., McIsaac, W. M., Walker, K. E., Estevez, V.: Inhibitors of monoamine oxidase. J. Pharm. Sci.57, 269–272 (1968 b).

    PubMed  Google Scholar 

  • Honecker, H., Coper, H., Fähndrich, C., Rommelspacher, H.: Tetrahydronorharmane (tetrahydro-β-carboline) in human blood platelets. J. Clin. Chem. Clin. Biochem.18, 133–135 (1980).

    PubMed  Google Scholar 

  • Hunkeler, W., Möhler, H., Pieri, L., Polc, P., Bonnetti, E. P., Cumin, R., Schaffner, R., Haefely, W.: Selective antagonists of benzodiazepines. Nature (London)290, 514–515 (1981).

    Google Scholar 

  • Lewinsohn, R., Glover, V., Sandler, M.:β-Phenylethylamine and benzylamine as substrates for human monoamine oxidase A: a source of some anomalies? Biochem. Pharmac.29, 777–781 (1980).

    Google Scholar 

  • Meller, E., Friedman, E., Schweitzer, J. W., Friedhoff, A. J.: Tetrahydro-β-carbolines: specific inhibitors of type A monoamine oxidase in rat brain. J. Neurochem.28, 995–1000 (1977).

    PubMed  Google Scholar 

  • Nelson, D. L., Herbet, A., Pétillot, Y., Pichat, L., Glowinski, J., Hamon, M.: [3H]Harmaline as a specific ligand of MAO A-I. Properties of the active site of MAO A from rat and bovine brains. J. Neurochem.32, 1817–1827 (1979).

    PubMed  Google Scholar 

  • Owen, F., Cross, A. J., Lofihouse, R., Glover, V.: Distribution and inhibition characteristics of human brain monoamine oxidase. Biochem. Pharmac.28, 1077–1080 (1979).

    Google Scholar 

  • Petursson, H., Bhattacharya, S. K., Glover, V., Sandler, M., Lader, M. H.: Urinary monoamine oxidase inhibitor and benzodiazepine withdrawal. Br. J. Psychiat.140, 7–10 (1982).

    Google Scholar 

  • Petursson, H., Reveley, M. A., Glover, V., Sandler, M.: Urinary MAO inhibitor in psychiatric illness. Psychiat. Res.5, 335–340 (1981).

    Google Scholar 

  • Peura, P., Kari, I., Airaksinen, M. M.: Identification by selective ion monitoring of 1-methyl 1, 2, 3, 4-tetrahydro-β-carboline in human platelets and plasma after ethanol intake. Biomed. Mass. Spectrom.7, 553–555 (1980).

    PubMed  Google Scholar 

  • Rommelspacher, H., Honecker, H., Barbey, M., Meinke, B.: 6-Hydroxytetrahydronorharmane (6-hydroxy-tetrahydro-β-carboline), a new active metabolite of indole-alkylamines in man and rat. Naunyn-Schmiedeberg's Arch. Pharmac.310, 35–41 (1979).

    Google Scholar 

  • Rommelspacher, H., Nanz, C., Borbe, H. O., Fehske, K. J., Müller, W. E., Wollert, U.: 1-Methyl-β-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding. Naunyn-Schmiedeberg's Arch. Pharmac.314, 97–100 (1980 a).

    Google Scholar 

  • Rommelspacher, H., Strauss, S., Lindemann, J.: Excretion of tetrahydroharmane and harmane into the urine of man and rat after a load of ethanol. FEBS Letts.109, 209–212 (1980 b).

    Google Scholar 

  • Sandler, M., Reveley, M. A., Glover, V.: Human platelet monoamine oxidase activity in health and disease: a review. J. clin. Path.34, 292–302 (1981).

    PubMed  Google Scholar 

  • Shoemaker, D. W., Cummins, J. T., Bidder, T. G., Boettiger, H. G., Evans, M.: Identification of harman in the rat arcuate nucleus. Naunyn-Schmiedeberg's Arch. Pharmac.310, 227–230 (1980).

    Google Scholar 

  • Sparks, D. L., Buckholtz, N. S.: 6-Methoxy 1, 2, 3, 4-tetrahydro-β-carboline: a specific monoamine oxidase-A inhibitor in CF-1 mouse brain. Neurosci. Lett.20, 73–79 (1980).

    PubMed  Google Scholar 

  • Youdim, M. B. H., Oppenheim, B.: The effect of tryptolines (1, 2, 3, 4-tetrahydro-β-carbolines) on monoamine metabolism and the platelet aggregation response in human platelets. Neuroscience6, 801 (1981).

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Vivette Glover

    Present address: Bernhard Baron Memorial Research Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Hospital, London, UK

  2. J. Liebowitz

    Present address: , 12,608 Davan Drive, 20904, Silver Spring, MD, USA

  3. Ines Armando

    Present address: Division de Endocrinologie, Hospital General de Niños “R. Gutierrez”, Gallo 1330, 1425, Buenos Aires, Argentina

Authors and Affiliations

  1. Bernhard Baron Memorial Research Laboratories and Institute of Obstetrics and Gynaecology, Queen Charlotte's Hospital, London, UK

    J. Liebowitz, Ines Armando & M. Sandler

Authors
  1. Vivette Glover
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Liebowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ines Armando
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Sandler
    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

Glover, V., Liebowitz, J., Armando, I. et al. β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications. J. Neural Transmission 54, 209–218 (1982). https://doi.org/10.1007/BF01254930

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01254930

Keywords

Search

Navigation