Iptakalim: A Potential Antipsychotic Drug with Novel Mechanisms?

Iptakalim is a novel putative adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener. In the brain, iptakalim is thought to act on the neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels. Because iptakalim demonstrates an action on the regulation of dopamine and glutamate release in the forebrain regions, we examined its potential antipsychotic efficacy in several preclinical tests. First, we show that iptakalim is effective in reducing amphetamine- and phencyclidine-induced hyperlocomotion as well as selectively disrupting conditioned avoidance responding. Next, we show that combined iptakalim and amphetamine treatment produces a reduction on prepulse inhibition of acoustic startle and this combined drug effect is also found with haloperidol, but not with clozapine. Finally, we show that iptakalim and clozapine preferentially increase c-Fos expression in the medial prefrontal cortex, nucleus accumbens and lateral septal nucleus, whereas haloperidol induces a greater increase in the nucleus accumbens, the dorsolateral striatum and lateral septal nucleus. Collectively, our findings indicate that iptakalim is likely to be a potential antipsychotic drug with distinct mechanisms of action. This study also suggests that neuronal and astrocytic plasma membrane and/or mitochondrial KATP channels may be a novel target that deserves attention for antipsychotic drug development. Future research using other sensitive tests is needed to confirm this property of iptakalim.

Social Cognition and Interaction Training (SCIT) for Individuals with Schizophrenia Spectrum Disorders in Outpatient Treatment Settings

The role of social cognition in severe mental illness (SMI) has gained much attention, especially over the last decade. The impact of deficits in socio-cognitive functioning has been found to have detrimental effects on key areas of day-to-day functioning in individuals with SMI, such as gaining and maintaining employment and overall experienced quality of life. Treatment of individuals with SMI is challenging, as the presentation of individual signs and symptoms is rather heterogeneous. There are several treatment approaches addressing deficits ranging from broader social and interpersonal functioning to neurocognitive and more intrapersonal functioning. As research in the domain of social cognition continues to identify specific deficits and its functional detriments, treatment options need to evolve to better target identified functional deficits. Social Cognition and Interaction Training (SCIT) was recently developed to address specific socio-cognitive deficits in an inpatient population of individuals with schizophrenia-spectrum disorders. This study applied SCIT in an outpatient SMI population as many deficits remain after individuals’ symptoms are less severe and overall functioning is more stable than during the acute inpatient phase of their rehabilitation. Specifically, this study has two objectives. First, to demonstrate that deficits in social cognition persist after the acute phase of illness has abated. Second, to demonstrate that these deficits can be ameliorated via targeted treatment such as SCIT. Data was gathered in local outpatient treatment settings serving a heterogeneous SMI population. Adviser: William D. Spaulding