Decoding
Schizophrenia:
New Classes of Schizophrenia Drugs in Development
By Daniel C. Javitt and
Joseph T. Coyle
Unless otherwise noted, the compounds mentioned below are in the early
stages of human testing. Their developers or producers are listed in
parentheses.
Stimulators of NMDA-type glutamate receptors aim to overcome the
signaling deficits that apparently contribute to many
schizophrenic symptoms.
Examples: Glycine (Medifoods), D-serine (Glytech). As natural
substances, both of them are sold, but they remain under evaluation
specifically for their value in treating schizophrenia.
Stimulators of AMPA-type glutamate receptors--also called ampakines--
may improve some aspects of memory and cognition in people with schizophrenia.
Example: CX516 (Cortex Pharmaceuticals)
Modulators of another class of glutamate receptors--metabotropic
receptors--can regulate glutamate release and potentially restore the balance
between the activity of NMDA and AMPA receptors. Example:
LY354740 (Eli Lilly)
Inhibitors of glycine transport reduce glycine removal from synapses,
which should increase signaling by NMDA receptors. Example:
GlyT-1 (NPS Pharmaceuticals and Janssen Pharmaceutica)
Stimulators of alpha 7 nicotinic receptors, the same receptors
activated by the nicotine in cigarettes, indirectly stimulate the brain's NMDA
receptors. Schizophrenics often smoke heavily, probably because the nicotine,
acting on alpha 7 receptors, helps them to focus. Example: DMXB-A
(University of Colorado Health Sciences Center)
Stimulators of D1 dopamine receptors are being developed mainly for
Parkinson's disease and have passed initial safety trials. They might also
correct dopamine deficiencies in schizophrenia, but clinical trials for that
purpose have not yet been performed. Example: ABT-431 (Abbott
Laboratories)
DANIEL C. JAVITT and JOSEPH T. COYLE have studied
schizophrenia for many years. Javitt is director of the Program in Cognitive
Neuroscience and Schizophrenia at the Nathan Kline Institute for Psychiatric
Research in Orangeburg, N.Y.,
and professor of psychiatry at the New York
University School of Medicine. His paper demonstrating that the
glutamate-blocking drug PCP reproduces the symptoms of schizophrenia was the
second-most cited schizophrenia publication of the 1990s. Coyle is Eben S.
Draper Professor of Psychiatry and Neuroscience at Harvard Medical School and
also editor in chief of the Archives of General Psychiatry. Both authors have
won numerous awards for their research. Javitt and Coyle hold independent
patents for use of NMDA modulators in the treatment of schizophrenia, and
Javitt has significant financial interests in Medifoods and Glytech, companies
attempting to develop glycine and D-serine as treatments for schizophrenia.
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