YALE TESTS PROMISING SCHIZOPHRENIA DRUG ON RATS

NEW HAVEN - Yale scientists drove rats mad with angel dust and discovered
that they could straighten out the psychotic rodents, using an experimental
drug that shifts brain chemicals but has no apparent side effects.

While human and rat brains are very different, the research suggests a
novel approach to treating schizophrenia, addiction and other psychiatric
disorders.

Current schizophrenia drugs cause unpleasant side effects and almost all
pose a long-term risk of triggering uncontrollable tremors.

Anti-psychotic medications also do not relieve poor attention span, jumbled
thoughts, disquieting social interactions and other symptoms of schizophrenia.

About 1 percent of the population has schizophrenia, which typically
emerges during young adulthood.

Results of the study, led by Bita Moghaddam, associate professor of
psychiatry and neurobiology at the Yale School of Medicine, are in today's
edition of the journal Science.

"It's impressive work," Columbia University schizophrenia researcher Jon
Horvitz wrote in an accompanying Science article. "This is a promising
avenue for a drug that attenuates schizophrenic symptoms."

Moghaddam emphasized that the research drug may not produce the same effect
in people, and that potential clinical use could be years away. The new
compound is being developed by Eli Lilly & Co., and is called LY354740.

Moghaddam and research associate Barbara W. Adams used phencyclidine,
(known as PCP or angel dust) because rats do not naturally develop
schizophrenia, or if they do, it's impossible to tell.

PCP is a hallucinogen known to cause psychosis in healthy humans, touching
off certain symptoms similar to schizophrenia, she said.

Rats under the influence of PCP engaged in frantic running and incessant
head rolling, and had disturbances in memory and attention.

Symptoms created by PCP in rats and humans are caused by elevated levels of
a brain chemical called glutamate, Moghaddam said. Glutamate acts
throughout the brain, switching on, or activating, neurons. Many
psychiatric disorders are associated with the glutumate system, she said.

Neurons possess many types of glutamate receptors, where the
neurotransmitter docks and delivers its message. PCP apparently blocks
certain glutamate receptors, increasing the action of glutamate at other
receptors. LY354740 attaches to a class of receptors called the
metabotropic glutamate receptors, or mGluRs.

This subtype of receptors controls the amount of glutamate used by neurons.
When stimulated by the new drug, the receptors returned glutamate levels to
normal.

The mGluRs themselves have subtypes of receptors, suggesting that drugs
similar to LY354740 might be effective against many disorders, Moghaddam said.

Unlike other anti-psychotic drugs, which work by blocking a
neurotransmitter called dopamine, the experimental drug did not affect the
dopamine system. Reducing dopamine action creates side effects, including
uncontrollable and untreatable tremors, known as tardive dyskinesia.

"The idea of the (mGluR) receptors is important," Moghaddam said. "Whether
LY354740 has a human use is not clear. Rat reactions are not necessarily
the same as humans'."

Checked-by: Mike Gogulski