Drugs that make you smarter

Moriguchi, S., Shioda, N., Yamamoto, Y., et al (2012). The T-type voltage-gated calcium channel as a molecular target of the novel cognitive enhancer ST101: enhancement of long-term potentiation and CaMKII autophosphorylation in rat cortical slices. Journal of Neurochemistry, 121(1):44-53 Details

Customer study highlights

We only use 10% of our brains – at least according to popular myth – fortunately, however, ‘cognitive enhancers’ are now here to help. Nutriceuticals, energy drinks, dietary supplements are all becoming increasingly available to aid in mental agility, concentration and memory performance. 

In medicine there are also reasons for the development of cognitive enhancers:  early symptoms of Alzheimer’s disease for example can be partly mitigated with drugs such as rivastigmine that boost synaptic levels of acetylcholine. 

Researchers from the Graduate School of Pharmaceutical Sciences in Tohku University have developed a novel cognitive enhancer – code-named ‘ST101’ – intended for the treatment of Alzheimer’s disease. Previous studies on ST101 have shown that is able to boost acetylcholine levels, while electrophysiological data also suggest that it aids in cellular processes related to learning and memory. 

In their most recent publication, Moriguchi et al show that incubation of ST101 with brain slices enhanced the protein expression of the enzymes, PKC and CaMKII. Both enzymes were elevated in the somatosensory cortex, while CaMKII alone was increased in the hippocampal CA1 region, a brain region intensely involved in learning and memory.  Furthermore, autophosphorylated forms of CaMKII were specifically increased. A major target of CaMPKII, the AMPA receptor subunit ‘GluR1’, was also found to be expressed in phosphorylated form in higher concentrations, indicating possible changes to excitatory neurotransmission pathways. These responses were inhibited with mibefradil, a T-type Ca2+ channel blocker. 

Electrophysiological recordings using a Nihon Kohden extracellular amplifier and a PowerLab data acquisition system revealed that ST101 enhanced cortical fEPSP slopes in response to stimulation, indicating a learning/remodelling effect, but this too was blocked with mibefradil. 

This study demonstrates a key mechanism of action of ST101 and also shows that T-type Ca2+ channels represent novel molecular targets for future development of cognitive enhancers.  

29 Jun 2012

By Matthew Goddard

Science Manager

Researcher, Dad and motorbike racer.

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