Antipsychotic treatments; focus on lurasidone

Sumiyoshi, Tomiki

doi:10.3389/fphar.2013.00102

Cited by 10 publications

(5 citation statements)

References 53 publications

(68 reference statements)

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“…In the present work, 0.5 mg/kg of flupenthixol produced a nonsignificant decrease in locomotor activity compared to the saline control group. The effect of these higher doses of flupenthixol on locomotor activity is not surprising as flupenthixol is a DAr antagonist and in humans, can induce extrapyramidal side effects (EPS) such as Parkinsonism, dystonia, and dyskinesia (Sumiyoshi, 2013). This is problematic and makes it difficult to differentiate a decrease in perseverative behavior from a sedative effect on movement.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

Tuplin¹,

Stocco²,

Holahan³

2015

Behavioral Neuroscience

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The noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-10-imine maleate (MK-801) has been shown to increase the probability of operant responding during extinction and reduce infralimbic prefrontal cortical activation, possibly modeling the cognitive dysfunction symptomology, and underlying cause, in patients with schizophrenia. The present study sought to determine if typical and/or atypical antipsychotics would attenuate the MK-801-induced behavioral perseveration and whether this would be associated with concomitant changes in phosphorylated ERK1/2 (pERK1/2) labeling in the infralimbic cortex (IL). Male, Long Evans rats were pretreated with the typical antipsychotic, Flupenthixol (0, 0.125, 0.25 or 0.5 mg/kg) or the atypical antipsychotic, aripiprazole (0, 0.3, 1.0, 3.0 mg/kg), then given 0.1 mg/kg MK-801 followed by a 60-min appetitive operant extinction session. Flupenthixol produced a dose-dependent decrease in MK-801-induced bar pressing behavior and locomotor activity and a dose-dependent increase in IL pERK1/2 labeling. Aripiprazole produced a U-shaped dose-response curve on MK-801-induced bar pressing behavior, a dose-dependent decrease in locomotor activity but no changes in IL pERK1/2 labeling. The attenuation of the MK-801-induced behavioral (bar pressing, locomotion) profile by Flupenthixol indicates a clear dopaminergic contribution to this behavior. The behavioral effect of aripiprazole may be due to its a) binding to presynaptic dopamine receptors at the midrange dose decreasing dopamine output and b) binding to postsynaptic dopamine receptors at the higher dose increasing dopamine tone. While both classes of antipsychotics can normalize perseverative behavioral symptoms, the underlying prefrontal cortical dysregulation seems to persist.

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Section: Discussionmentioning

confidence: 99%

Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

Tuplin¹,

Stocco²,

Holahan³

2015

Behavioral Neuroscience

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“…It should be noted that no data were presented in that study (Goldberg et al 2007) as to whether schizophrenia patients not receiving AAPDs would have elicited the same degree of improvement as that in treated patients. In fact, lurasidone, an AAPD with high affinity for 5-HT 1A receptors, has been reported to dose-dependently improve cognitive function in a placebo-controlled double-blind study (Harvey et al 2013;Sumiyoshi 2013).…”

Section: Pharmacological Treatments Of Cismentioning

confidence: 99%

Cognitive Impairment in Schizophrenia

Sumiyoshi

2013

Encyclopedia of Psychopharmacology

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Cognitive deficits in schizophrenia; Cognitive disturbances of schizophrenia Definition Patients with schizophrenia exhibit about a 1-2.5SD decline in a range of cognitive domains, e.g., several types of memory, executive function, verbal fluency, and attention/information processing. The cognitive impairment is measured by neuropsychological tests. Backgrounds The concept of cognitive impairment in schizophrenia (CIS) can be traced back to "dementia praecox" coined for the illness by E. Kraepelin. Also, it is noteworthy that E. Bleuler, who assumed the change of brain function in schizophrenia, included disturbances (loosening) of association in the core symptoms of the disease. More recently, these traditional views regarding CIS have been quantified by objective measures, mainly neuropsychological tests. Several cognitive domains profoundly impaired ("differential deficits") in schizophrenia include verbal memory, executive function, verbal (category) fluency, and attention, as indicated by meta-analytic studies (e.g., Reichenberg and Harvey 2007). Assessments Some internationally standard neurocognitive test batteries covering key cognitive domains have been developed for the assessment of therapeutic effects. These include MATRICS Consensus Cognitive Battery (MCCB) (Nuechterlein and Green 2006), the CogState Schizophrenia Battery, and the Brief Assessment of Cognition in Schizophrenia (BACS) (Harvey 2013). Figure 1 demonstrates the scores of the MCCB Japanese version in patients with schizophrenia, showing impaired performance on tests of information processing/speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition.

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“…It is reported that adjunctive treatment with selective 5-HT 1A receptor (partial) agonists, e.g., tandospirone or buspirone, was associated with improvements in some types of cognitive function in patients with schizophrenia (Sumiyoshi et al, 2001b , 2007 ; Sumiyoshi and Higuchi, 2013 ). These observations provide the basis for the ability of 5-HT 1A receptor stimulation to enhance cognition, a therapeutic approach that have promoted the development of novel antipsychotic drugs (Sumiyoshi, 2013 ; Sumiyoshi et al, 2013 ).…”

Section: Introductionmentioning

confidence: 96%

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

Uehara

Matsuoka²,

Sumiyoshi

2014

Front. Behav. Neurosci.

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Rationale: Augmentation therapy with serotonin-1A (5-HT1A) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production.Objectives and methods: The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia.Results: Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment.Conclusions: These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT1A agonism improve cognitive impairment of schizophrenia and related disorders.

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Antipsychotic treatments; focus on lurasidone

Cited by 10 publications

References 53 publications

Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

Cognitive Impairment in Schizophrenia

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

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