Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics...Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.展开更多
Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in pat...Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.展开更多
文摘Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.
基金supported by thegrant of Stanley Medical Research Institute(No.02I-005),USA
文摘Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.
