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Screening Services for Pre-Clinical Development of Neuro-Pharmaceuticals and Safety Pharmacology

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New Electrophysiological Database for the Screening of CNS Drugs

16 March 2010: The combination of these optimised methods permits the precise electrophysiological description and differentiation of the effects of substances on the central nervous system. Depending on the brain region tested and the substance with which the neuronal network is chemically stimulated, the
electrical action potential pattern changes distinguishable in a way comparable with the changes
visible on an EEG. The advantage of this method is that most of the physiological in vivo targets of
potential drugs are present in the in vitro system. This opens the way for the discovery of completely
new and unexpected mechanisms of action. Using complex methods of data analysis the company’s
scientists have identified those parameters of the activity patterns which are of particular
significance in the analysis of activity changes. They were also able to show that even substances
with similar mechanisms of action can cause differentiable changes in activity patterns as a result of
differences in the structure of receptor subtypes in different tissues.

The current version of this first completed substance data base documents the effect of substances
on the frontal cortex of the mouse. This region of the brain plays a crucial role in all cognitive
processes. The database contains substances from all the main classes, classified according to G
protein‐coupled and ionotropic receptors, ion channels, gap junctions and the enzymes of various
signalling cascades. Many of these substances are used both in the treatment of common CNS
conditions such as Alzheimer’s, epilepsy, depression and anxiety disorders and in pain relief. As all
biological subsystems, receptors etc. are present in the primary neuronal cell cultures, this
broadband sensor system reliably picks up even those biological mechanisms not previously
attributed to a particular substance. This is especially important in the light of the fact that
completely new therapies are currently being urgently sought for a wide range of illnesses.

As CNS drugs work differently in different regions of the brain, NeuroProof GmbH is currently
developing three other databases of substance‐specific activity profiles for the spinal cord, the
hippocampus and the hypothalamus. The spinal cord is of particular interest in the development of
analgesics and neuroregenerative substances, the hippocampus in substances which influence
learning and memory (this is of high interest for Alzheimer’s disease), and the hypothalamus plays a
major role in anxiety, among other things.

NeuroProof is the world leader in the long term cultivation of primary neurone glia co‐cultures on
MEA neurochips for use in commissioned studies.