A randomized, double-blind, placebo-controlled study demonstrated that members of a sarcosine (2 g/day) group showed greater reductions in their Positive and Negative Syndrome Scale (PANSS) total scores than members of a placebo group or D-serine (2 g/day) group, suggesting that sarcosine is superior to D-serine in that benefits both patients with long-term stable disease and also acutely ill persons with schizophrenia .
Furthermore, a randomized, double-blind study reported that sarcosine (2 g/day) alone was effective in the treatment of acutely symptomatic drugfree patients with schizophrenia.
Nonetheless, all these findings suggest that GlyT-1 inhibition could be a novel pharmacotherapeutic target for enhancing cognitive dysfunction in schizophrenia and several clinical trials are underway with very promising results.
Gaining a better understanding of the role of GlyT-1 in the treatment of cognition in schizophrenia is expected to provide new perspectives for treating this disorder. The pharmacological modulation of glycine modulatory sites on NMDA receptors by GlyT-1 inhibitors could be beneficial in the treatment of the cognitive deficits and psychosis associated with schizophrenia and other psychiatric conditions.
Galantamine, which acts as both a cholinesterase inhibitor and a nicotinic receptor modulator had the best result. The cognitive effects of galantamine may be accentuated by its nicotinic allosteric agonist action, which can improve attention and memory. Furthermore, galantamine appears to more powerfully elevate frontal cortical dopamine levels than cholinesterase inhibitors such as donepezil. This biological effect may be significant since frontal dopaminergic deficits have been proposed to underlie cognitive impairment in schizophrenia.
Importantly, significant improvement in attentional set shifting was seen. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.
Patient with schizophrenia manifest signs of a dysregulation of the NPY system. Extensive preclinical studies suggest that the neuropeptide Y (NPY) counteracts the behavioral consequences of stress and anxiety to and maintain emotional homeostasis. Thus it is involved in stress regulation and coping.
Treatment of Cognition in Schizophrenia
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