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Discovery of novel orally available painkillers targeting the vanilloid receptor 1 in the peripheral nervous system


Through a concerted research effort involving molecular cloning, stable cellular expression, and robotic screening of targeted combinatorial chemical libraries, Dr. Olah has discovered new classes of analgesic agents. Some blocks the ion channel, others the agonist binding function of the vanilloid receptor 1 (TRPV1), a key molecule expressed in pain-sensing C-fibre primary afferent neurons, but previously not targeted specifically with drug treatment.

The primary goal is to complement or replace current NS AID, opiate and adjuvant treatments with new non-narcotic drugs specifically targeting TRPV1 and thereby intercept pain signals at the periphery before they enter the central nervous system. Through joining to the BRC of HAS in Szeged, Hungary, Dr. Olah will perform structure-activity optimisations of lead compounds by cell-based assays, which can efficiently treat severe pain conditions. The drug discovery process will be complemented by in silico channel modelling and docking studies and is expected to result in invention of new chemical entities.

The best compounds will be synthesized in large scale and evaluated for in vivo efficacy in a two-tiered system. The first level employs conventional rodent analgesic tests on two species; the second level includes naturally occurring veterinary canine cancer and arthritis models. The combination have proven enormous predictive value for performance in human, including treatment of cancer and arthritis pain, previously approached by Dr. Olah employing an innovative drug, which currently is in clinical trial. Compounds exhibiting strong analgesic activity will be subjected to toxicity, pharmacology, and efficacy studies, required for human analgesia trial.

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