The beta-carboline alkaloids are predominant constituents of several natural products
including plants, marine and microbial sources. The psychoactive properties of Banisteriopsis capi, an ingredient of famous hallucinogenic drink „ayahuasca“, and Peganum harmala, the traditional herbal remedy as emmenagogue & abortifacient, have been linked to
inhibition of monoamine oxidases (MAO-A & B) by their beta-carboline harmala alkaloid
constituents. Due to central role of MAOs in the metabolism of dietary as well as
neurotransmitters metabolism, these enzymes represent attractive drug targets in the
pharmacological therapy of neurodegenerative diseases and depression. A series of
beta-carboline analogs were assayed in vitro as inhibitors of recombinant human MAO-A and MAO-B isoforms. The analogs were tested
at saturating and varying concentrations of the substrates for evaluation of kinetic
characteristics of inhibition of specific enzyme isoform. Most of the compounds showed
more potent and selective inhibition of MAO-A. A few beta-carboline analogs, selective
against MAO-B, were also identified. The results have been further analyzed for structure
activity relationship and should be useful in designing the MAO inhibitors with desired
therapeutic characteristics. Recent efforts toward the development of MAO inhibitors
are focused on selective MAO-A or MAO-B inhibitors. Selective MAO-A inhibitors are
effective in the treatment of depression whereas MAO-B inhibitors are useful for the
treatment of Alzheimer's disease and Parkinson's disease. Acknowledgements: Supported by the National Center for Complementary and Alternative Medicine (NCCAM),
National Institute of Health, Grant No. 5R21AT003409–02.
