Tuesday, September 16, 2008

Rethinking Schizophrenia

From the September 15th edition of Chemical and Engineering News (C&EN):
Advances could spur treatments for more symptoms than current drugs address

By Carmen Drahl

WHEN ACCOUNTS of schizophrenia began to emerge in the 1800s, institutionalization was the most common treatment for patients suffering from the disease. Despite significant advances in therapy, many of today's patients still find fitting into society a big challenge. Although iconoclastic 1960s psychiatrist Ronald D. Laing once wrote "Schizophrenia cannot be understood without understanding despair," the prevailing sentiment at last month's American Chemical Society national meeting in Philadelphia was one of hope. Researchers have learned more about the pathways that underpin schizophrenia, and those advances have led to drugs in clinical trials that reflect new approaches to treating the disease.

Session organizer John E. Macor, executive director of neuroscience discovery chemistry at Bristol-Myers Squibb (BMS), in Wallingford, Conn., told C&EN that existing medications for schizophrenia, known as antipsychotics, do not remedy all of the disease's symptoms. Speakers at the Division of Medicinal Chemistry-sponsored symposium advocated moving beyond established drugs, which are all aimed at dopamine neurotransmission. They argued that focusing on new targets, such as the glutamate neurotransmitter system, a nicotinic acetylcholine receptor, or a signaling pathway mediated by cyclic nucleotides, might tackle a wider range of symptoms.

In her stage-setting overview for the session, Judith A. Siuciak, principal scientist for neuroscience biology at BMS, characterized schizophrenia by what she described as positive, negative, and cognitive symptoms. Commonly prescribed drugs ease positive symptoms, which include hallucinations and disorganized speech. However, she said, the drugs are less effective at eliminating negative symptoms, such as lack of motivation and inability to experience pleasure, and cognitive symptoms, which include impairments to memory and decision-making.

"The medications that we have are only partially effective," concurs Robert K. Heinssen, deputy director of the National Institute of Mental Health's (NIMH's) Division of Services & Intervention Research, who did not attend the symposium but spoke with C&EN beforehand. What's more, he adds, not all patients respond equally well to the drugs. Even with medication, schizophrenia sufferers can be withdrawn and have trouble processing information, so "these patients are overwhelmed by the competing demands of our environment," he says.
Bold emphasis within the article is mine. To read the entire article, click here.

Selective Drug Pfizer's drug candidate for schizophrenia (stick model) blocks a specific phosphodiesterase enzyme. Protein surfaces contacting the drug are shown in a space-filling format. Amino acids and a water molecule that make contact with the drug are shown in ball-and-stick form.

Image courtesy of Eric Marr, Jayvardhan Pandit & Xinjun Hou/Pfizer.

New drug candidates for the treatment of schizophrenia.
Click on the image to enlarge it.

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