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Publications (60)
The above article from Human Psychopharmacology , first published on 25 January 2012 in Wiley OnlineLibrary ( onlinelibrary.wiley.com ), and in Volume 90, pp. 90‐100, has been retracted by agreement between the authors, the journal Editor in Chief, David Baldwin, and John Wiley & Sons Ltd. The retraction has been agreed following an investigation b...
This article reviews the recent evidence for therapeutic strategies for patients with treatment-resistant schizophrenia (TRS) not responding to or only partially responding to clozapine.
A number of pharmacological and nonpharmacological biological approaches for clozapine-resistant TRS have been evaluated in clinical trials. Among these, the evide...
AimsThe purpose of this study was to evaluate the long-term effectiveness and safety of blonanserin, a second-generation antipsychotic drug developed in Japan, in patients with first-episode schizophrenia. Methods
Twenty-three antipsychotic-naive patients with first-episode schizophrenia were treated within an open-label, 1-year, prospective trial...
All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side-effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripher...
Blonanserin was developed as an antipsychotic drug in Japan and approved for the treatment of schizophrenia. It belongs to a series of 4-phenyl-2-(1-piperazinyl)pyridines and acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors. Blonanserin has low affinity for 5-HT2C, adrenergic α1, histamine H1, and muscarinic M1 receptors, bu...
Blonanserin was developed in Japan in 2008 as an antipsychotic drug. It has high affinity for dopamine D2/3 and serotonin 5-HT2A receptors, but shows low affinity for adrenergic alpha1, histamine H1, and muscarinic M1 receptors. Several short-term double-blind trials demonstrated that blonanserin was well tolerated and had equal efficacy to haloper...
Purpose of review:
The current article provides a brief review of the clinical efficacy and safety outcomes from selected phase I and II clinical trials of compounds in development acting on targets beyond the dopamine D2 receptor in patients with schizophrenia.
Recent findings:
A number of experimental pharmacological targets have been studied...
The introduction of second-generation antipsychotics (SGAs), heralded by clozapine in 1990, represented an important advance in the pharmacologic treatment of schizophrenia. However, several recent comparative effectiveness trials found that non-clozapine SGAs provided little or no advantage in efficacy over first-generation antipsychotics, and all...
Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychose...
The purpose of this study was to evaluate the effects of blonanserin, a novel antipsychotic, on cognitive function in first-episode schizophrenia.
Twenty-four antipsychotic-naïve patients with first-episode schizophrenia participated in the study. Blonanserin was given in an open-label design for 8 weeks. The Brief Assessment of Cognition in Schizo...
The high use of long-term benzodiazepines (BZDs) with second-generation antipsychotics (SGAs) has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual reduction or discontinuation of daytime BZD use on cognitive function and quality of life (QOL) in patients w...
The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophreni...
Dramatic growth of research in the area of pharmacotherapy for psychotic disorders has advanced our understanding of the neurobiology of these illnesses and of the medications used to treat them. The advent of second-generation antipsychotics (SGAs) represents an incremental advance in the treatment of psychosis, and in many parts of the world SGAs...
IntroductionTherapeutic goals of acute treatmentPharmacological agentsPractical clinical issuesTreatment of different stages of illnessConclusions
Antipsychotic medications remain the foundation of pharmacological treatment of schizophrenia. Although there has been significant progress over the past decade resulting in the introduction of several new agents, all currently available antipsychotics modulate brain dopamine systems and can essentially be classified into two groups: conventional (...
The neurodevelopmental hypothesis of schizophrenia posits an interaction between multiple susceptibility genes and one or more environmental insults in early life, resulting in altered brain development and the emergence of psychosis in early adulthood. Based on this framework, it has been argued that most neuropathological deficits observed in pos...
The advent of second-generation antipsychotics (SGA) in the wake of clozapine, the prototype for atypical antipsychotics, represents a breakthrough in the pharmacologic treatment of schizophrenia. There is growing evidence that most of the SGA can offer advantages over first-generation antipsychotics within the effective dose range, such as improve...
The treatment of schizophrenia has evolved over the past half century primarily in the context of antipsychotic drug development. Although there has been significant progress resulting in the availability and use of numerous medications, these reflect three basic classes of medications (conventional (typical), atypical and dopamine partial agonist...
The neurodevelopmental hypothesis of schizophrenia posits an interaction between multiple susceptibility genes and one or more environmental insults in early life, resulting in altered brain development and the emergence of psychosis in early adulthood. Based on this framework, it has been argued that most neuropathological deficits observed in pos...
A mouse strain has been developed that expresses low levels of the NR1 subunit of the NMDA receptor. These mice are a model of chronic developmental NMDA receptor hypofunction and may therefore have relevance to the hypothesized NMDA receptor hypofunction in schizophrenia. Many schizophrenia patients show exaggerated behavioral and neuronal respons...
The fact that chronic administration of typical and atypical antipsychotic drugs is required for optimal therapeutic response suggests that drug-induced adaptive neurochemical changes contribute to their mechanism of action. In the present study, the effects of chronic and acute haloperidol and olanzapine were compared on ketamine-induced activatio...
Despite great progress in basic schizophrenia research, the conclusive identification of specific etiological factors or pathogenic processes in the illness has remained elusive. The convergence of modern neuroscientific studies in molecular genetics, molecular neuropathology, neurophysiology, in vivo brain imaging, and psychopharmacology, however,...
A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting f...
The interaction of glutamatergic and dopamine neurotransmission is thought to have relevance to both the pathophysiology and pharmacotherapy of schizophrenia. For example, subanesthetic doses of the N-methyl-D-aspartate receptor (NMDA-R) antagonist ketamine induce schizophrenia-like behavioral effects in humans and both behavioral and brain metabol...
The ability of subanesthetic doses of N-methyl-D-aspartate (NMDA) antagonists to induce positive, negative, and cognitive schizophrenia-like symptoms suggests that reduced NMDA receptor function may contribute to the pathophysiology of schizophrenia. An increasing body of evidence indicates that antipsychotic drugs, especially those with "atypical"...
Although the pathophysiology of schizophrenia remains unclear, behavioral effects in humans induced by N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, provide direction for formulating new pharmacologic models of the illness. The purpose of the present study was to clarify the roles of NMDA receptor antagonism, as well as dopamine-releas...
Subanesthetic doses of NMDA receptor antagonists induce positive, negative and cognitive schizophrenia-like symptoms in healthy humans and precipitate psychotic reactions in stabilized schizophrenic patients. These findings suggest that defining neurobiologic effects induced by NMDA antagonists could guide the formulation of experimental models rel...
Dysregulation in the negative feedback of the hypothalamus-pituitary-adrenal (HPA) system is observed in a subgroup of major depression. Recent studies have postulated that tricyclic antidepressant treatment increases the glucocorticoid receptor (GR) in the brain and that such GR up-regulation normalizes the hyperactivity of HPA systems. The GR is...
The molecular mechanism of the action of antidepressants beyond the receptor level has not yet been elucidated. We have investigated the effects of long-term treatment with desipramine on the phosphorylation state of microtubule-associated protein 2 (MAP2) and microtubule assembly in the rat cerebral cortex. Phosphorylation of MAP2 was detected by...
We examined the effects of chronic treatment with several types of antidepressants on microtubule assembly and phosphorylation of microtubule-associated proteins (MAPs) in the rat cerebral cortex. The microtubule assembly was monitored in turbidity at 350 nm using a spectrophotometer. Chronic but not acute treatment with desipramine (DMI), maprotil...
