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perspective: Akira Sawa and Solomon H. Snyder GENETICS: Two Genes Link Two Distinct Psychoses Science 2005; 310: 1128-1129 [Summary] [Full text] [PDF]

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PDE4 inhibitors: Potential schizophrenia therapeutics?

David Gurwitz, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel   (17 February 2006)

PDE4 inhibitors: Potential schizophrenia therapeutics? 17 February 2006
David Gurwitz Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel Respond to this E-Letter: Re: PDE4 inhibitors: Potential schizophrenia therapeutics?	A key problem with current anti-psychotic medications is that they do very little to improve the negative symptoms of schizophrenia patients (1). Sawa and Snyder rightfully suggest here that in view of the new findings on the involvement of DISC1 in schizophrenia, new therapeutics might be envisaged along the route of inhibiting phosphodiesterase-4 (PDE4) activity. Indeed, it is noteworthy that in animal studies, the selective PDE4 inhibitor rolipram could reverse amphetamine-induced reductions in auditory-evoked potentials, one of the common features of schizophrenia (2). Further animal studies demonstrated that rolipram could attenuate the disruptive effect of MK-801 on latent inhibition (3), reverse scopolamine-induced memory deficits (4), and improve cognition in mice double transgenic for amyloid precursor protein and presenilin-1 mutations (5). These studies indicate that rolipram, or similar PDE4 inhibitors, have a genuine potential as add-on therapeutics, in conjunction with current medications, for treating the negative symptoms of schizophrenia and for improving memory function in Alzheimer's disease. This potential should be carefully examined. References 1. H. J. Moller, Management of the negative symptoms of schizophrenia: new treatment options, CNS Drugs 17, 793-823 (2003). 2. C. R. Maxwell, S. J. Kanes, T. Abel, S. J. Siegel, Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications, Neuroscience 129, 101-107 (2004). 3. J. A. Davis, T. J. Gould, Rolipram attenuates MK-801-induced deficits in latent inhibition, Behav Neurosci. 119, 595-602 (2005). 4. K. Rutten, J. Prickaerts, A. Blokland, Rolipram reverses scopolamine- induced and time-dependent memory deficits in object recognition by different mechanisms of action, Neurobiol Learn Mem. Oct. 19 2005 [Epub ahead of print]. 5. B. Gong, O. V. Vitolo, F. Trinchese, S. Liu, M. Shelanski, O. Arancio, Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment, J. Clin. Invest. 114, 1624- 1634 (2004).