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Natural terpenoids as a promising source for modulation of GABAergic system and treatment of neurological diseases

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Abstract

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter reducing neural excitability in the mammalian central nervous system (CNS) with three subclasses of receptors. Several conventional drugs and compounds modulate the GABAergic system, demonstrating different pharmacological effects. In this review, interactions of natural terpenoids with the GABAergic system are highlighted with relation to disorders like anxiety, insomnia, convulsion, pain, and cognitive deficits. Terpenoids with various structures affect the function of the GABAergic system via dissimilar mechanisms. Most of the discussed compounds interact with GABA receptors, but especially with the GABAA subtype. This may be due to the fact that researchers tend to assess the interaction of compounds using GABAA receptors. However, bilobalide, a sesquiterpene, showed anticonvulsant properties through the activation of glutamic acid decarboxylase (GAD) enzyme, which is a key enzyme in biosynthesis of GABA. Therefore, further studies evaluating and comparing terpenoids of different classes and their interaction with the GABA system, along with their pharmacokinetic properties, could be worthwhile in future studies.

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Authors and Affiliations

  1. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Azadeh Manayi

  2. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Nabavi

  3. Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia, Italy

    Maria Daglia

  4. Department of Pharmacognosy, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran

    Samineh Jafari

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  1. Azadeh Manayi
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  2. Seyed Mohammad Nabavi
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  3. Maria Daglia
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  4. Samineh Jafari
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Correspondence to Samineh Jafari.

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Manayi, A., Nabavi, S.M., Daglia, M. et al. Natural terpenoids as a promising source for modulation of GABAergic system and treatment of neurological diseases. Pharmacol. Rep 68, 671–679 (2016). https://doi.org/10.1016/j.pharep.2016.03.014

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