Neuropeptide S (NPS) may help in treating schizophrenia
Jun 22, 2006 - 11:40:37 PM

A small protein in the brain that has only recently been discovered and, paradoxically, induces both profound wakefulness and a less anxious state, may represent a novel target for the treatment of psychotic behavior and schizophrenia, according to new research presented at the 6th International Congress of Neuroendocrinology (ICN 2006).

Neuropeptide S (NPS), so named by Rainer K. Reinscheid, Ph.D., assistant professor, Program in Pharmaceutical Sciences, University of California, Irvine, is produced by a small cluster of cells in the brainstem, yet its specialized receptors are found in several areas of the brain, including those that are associated with the regulation of arousal, sleep and wakefulness, anxiety, appetite, learning and memory. Dr. Reinscheid and his colleagues reported finding the new neuropeptide just last year and described animal studies showing how binding of NPS to its receptors on the surfaces of neurons promotes strong arousal, suppresses all phases of sleep and lessens anxiety in stressful or unfamiliar situations.

Now, at ICN 2006, Dr. Reinscheid's group reports how NPS also can reduce the biochemical and behavioral symptoms of schizophrenia in an established animal model for this mental illness that affects some 2 million Americans. Animals pretreated with NPS before receiving a drug that normally induces psychotic-like behaviors did not develop the signature behavioral symptoms and neurochemical features of schizophrenia, reported Naoe Okamura, M.D., Ph.D., who is a co-worker of Dr. Reinscheid at the University of California, Irvine.

"Although preliminary, our animal studies indicate the NPS receptor should be explored as a target for the development of novel antipsychotic drugs. Whether molecules activating the NPS system will prove to be better drugs than others used to treat the symptoms of schizophrenia remains to be seen. We still have a very long way to go before proving it can alleviate symptoms in humans as we've seen it do in rodents," said Dr. Reinscheid.

"We've already seen how NPS is unique, being able to modulate both arousal and stress responses. So it could potentially be a target for drugs to treat anxiety and, interestingly, both insomnia and narcolepsy," he added.

The receptor for NPS belongs to a class of those with similar structure called G protein-coupled receptors. Collectively, they have a hand in modulating most every physiological process in the body and brain. Moreover, according to Dr. Reinscheid, about 40 percent of drugs on the market target the function and various actions of these receptors.

Dr. Reinscheid's lab is only beginning to understand how the NPS system works. Thus far, the team's research suggests it acts much like an excitatory neurotransmitter that initiates an impulse by the receiving neuron. Currently, the team is looking at whether natural mutations in the genes of NPS and its receptor might be associated with mental disorders and developing animal models that lack parts of the NPS system in order to better understand its functions.

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