First Administration of Cytidine Diphosphocholine and Galantamine in Schizophrenia: A Sustained alpha7 Nicotinic Agonist Strategy

The alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) has been proposed as a promising target for medication development in schizophrenia. The converging evidence implicating ‘‘hypofunction’’ of this receptor in schizophrenia includes epidemiological data on the high prevalence of smoking, electrophysiological data, genetic linkage and association studies, and postmortem studies.{1-10} Schizophrenic patients and their closely related biological relatives, including unaffected ones, manifest a deficit in inhibitory auditory gating that is inherited in an autosomal dominant manner and seems to result from diminished expression of the  alpha7 nAChR, a cation channel receptor that is gated by acetylcholine (ACh), in the hippocampus.{4,}{11} This deficit is reflected in a failure to blunt the amplitude of the positively evoked potential appearing about 50 milliseconds (P50 wave) after the second of a pair of identical auditory stimuli presented 500 milliseconds apart relative to the amplitude evoked in response to the first stimulus of the pair. Linkage and association studies implicate the gene for the alpha7 nAChR polypeptide subunit located in the q13-q14 region of chromosome 15, referred to as CHRNA7, with schizophrenia.{6-8} Autopsy studies support diminished expression of the alpha7 subunit in the frontal cortex, hippocampus, and thalamus in patients with schizophrenia.{9,}{10,}{12}
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