Spider Neurotoxins as Modulators of NMDA Receptor Signaling

Abstract

Molecules that selectively act on N-methyl-D-aspartate (NMDA) receptors may have a multidirectional effect by modulating the activity of NMDARs, affecting their active sites as well as by changing the composition of their subunits. The results of the clinical trials conducted so far in mood disorders and schizophrenia indicate that such agents may become new effective drugs for the treatment of these diseases. Number of spider neurotoxins e.g. ctenitoxins extracted from Phoneutria sp. venom act as potent and selective NMDAR blockers that do not disturb cortical and hippocampal glutamate signaling, LTP generation and synaptic neurochemistry. Possibly this intriguing kind of promising neuroregulatory peptides and polyamines can be clinically applicable in a wide spectrum of neuropsychiatric disorders, including epilepsy, neurotrauma and ischemic injuries. These novel medications can potentially be helpful in the future treatment of stroke and several neurodegenerative diseases.