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Updated: Apr 4, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
The N-Acylpolyamine Structure Assigned as Parawixin10 Does Not Display Positive Allosteric Modulatory Activity in
Yasaman Doroudian1, Melissa Schepers2,3, Tim Vanmierlo2,3
1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen OE 2100, Denmark.
Abstract:
Enhancing glutamate (Glu) uptake by positive allosteric modulation of excitatory amino acid transporter subtype 2 (EAAT2) is an attractive strategy to enable neuroprotection. However, while the EAAT field is rich in reports on inhibitors, enhancing EAAT2 protein dynamics is a much more difficult objective. A natural product approach reported that a spider venom HPLC fraction, number 10, showed neuroprotective effects. It was referred to as parawixin10, and later the structure of the key component responsible for the neuroprotective action was disclosed to be an N-acylamine, compound 2. We have resynthesized the N-acylamine 2 (parawixin10) and show here that this compound does not enhance Glu uptake in a wide range of radioligand binding assays, nor does it, in our hands, show any neuroprotective effect in a dose-dependent, statistically significant way.
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