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Abbott Researchers Target Neuronal Nicotinic Receptors for Treatment of Pain and Cognition
Date:11/1/2007

otics bind to D3 receptors. However, current antipsychotic medications are non-selective for the D3 receptors and have little effect on negative symptoms (i.e., apathy, lack of emotion, poor or nonexistent social functioning) or on cognitive deficits (i.e., disorganized thoughts, difficulty concentrating and/or following instructions, difficulty completing tasks, memory problems).

Abbott's pre-clinical, selective D3 compounds show high potency and selectivity for D3 receptors and have demonstrated efficacy in a number of preclinical models assessing antipsychotic efficacy. In preclinical studies, they do not induce secondary negative symptoms, extrapyramidal side effects (physical symptoms that can occur in individuals taking antipsychotic medications) or neuroendocrine disturbances associated with current agents.

ABT-925 promises to be a potent and selective dopamine D3 receptor antagonist, currently in early Phase II clinical trials for schizophrenia. The pharmacological profile of ABT-925 suggests that it will be differentiated from current antipsychotic agents by a broad range of therapeutic efficacy and diminished on-target and off-target (e.g. D2, H1 and Alpha 1 adrenoceptor) side effects.

TRPV1 Receptor Program

The TRPV1, or vanilloid receptor, plays an important role in mediating the body's response to a variety of pain stimuli, including heat and changes in pH levels, as well as a variety of mediators of inflammation that are released in the body following tissue damage. Abbott has identified a number of compounds that may have the ability to elicit relief across a broad spectrum of pain states. The lead compounds have demonstrated efficacy comparable to morphine across a number of different pre-clinical pain models -- including osteoarthritis, post-operative and cancer pain.

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