March 21, 2016

Putting schizophrenia to bed

A new compound developed at Vanderbilt treats multiple symptoms of schizophrenia in an animal model, without causing sedation.

by Marilyn Holt


Sleep abnormalities are commonly reported in schizophrenia patients, and growing evidence suggests that correcting these abnormalities may lead to improvements in other schizophrenia symptoms.

While some currently available antipsychotic drugs alleviate these sleep disruptions, they also cause sedation, which may limit positive effects on cognitive functions.

To develop more effective therapies, Carrie K. Jones, Ph.D. and colleagues have selectively targeted the M4 muscarinic acetylcholine receptor subtype, which modulates mood, cognition, and sleep architecture, by using positive allosteric modulators (PAMs).

Jones and colleagues found that the M4PAM, VU0467154, increased sleep duration in rats without disrupting sleep quality or causing drowsiness during waking periods. VU0467154 also normalized cortical electroencephalography (EEG) disruptions in an animal model of schizophrenia.

These findings, recently described in Neuropharmacology, indicate that VU0467154 has the potential to treat multiple symptoms of schizophrenia without causing the sedation observed with other antipsychotic drugs. If so, this could lead to improved outcomes and quality of life for this patient population.

The research was supported in part by National Institutes of Health grants MH086601, MH073676, MH087965, MH093366 and AstraZeneca.

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