Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement

Possible Relationship between Combined Plasma Concentrations of Risperidone plus 9-Hydroxyrisperidone and Extrapyramidal Symptoms

“…Risperidone also influences noradrenergic neurons; for example, risperidone has the inhibitory effect of a noradrenaline transporter [9] and has been reported to show · 1 -and · 2 -adrenoceptor-antagonistic effects [10]. Further, we have found that risperidone improves the negative symptoms of schizophrenia by influencing the noradrenergic neurons [11]. Risperidone is extensively metabolized in the liver by cytochrome P450 3A4 as well as 2D6 into a major active metabolite, 9-hydroxyrisperidone [12,13], which is the predominant circulating molecule and appears to be of approximately equal efficacy as the parent compound with respect to receptor-binding activity and some of its effects on animals [14].…”

Associations between plasma levels of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) and negative symptoms or cognitive impairments in early‐stage schizophrenia

“…Actually, we reported that plasma MHPG levels in patients with first-episode schizophrenia were significantly lower than those in healthy controls, and treatment with atypical antipsychotic drugs such as risperidone, olanzapine, and aripiprazole significantly increased plasma MHPG levels, which was associated with the improvement of negative symptoms of schizophrenia (Yoshimura et al, 2000a(Yoshimura et al, , 2008Hori et al, 2007). We demonstrated in a previous study that atypical antipsychotic drugs inhibited noradrenaline transporters (Yoshimura et al, 2000b(Yoshimura et al, , 2001(Yoshimura et al, , 2005. Taking these findings into account, we conclude that atypical antipsychotic drugs partially improve negative symptoms and cognitive impairments of schizophrenia by enhancing noradrenergic neurons via inhibiting NAT.…”

“…Since a number of studies have suggested that plasma levels of MHPG and HVA parallel concentrations in the brain and cerebrospinal fluid (CSF) (Nagaoka et al, 1997;Yoshimura et al, 2000b), we chose plasma samples to evaluate the catecholaminergic dynamics in the brain. Hypofunction of noradrenergic neurons have been associated with the impaired working memory.…”

Addition of risperidone to sertraline improves sertraline‐resistant refractory depression without influencing plasma concentrations of sertraline and desmethylsertraline

“…Furthermore, our previous findings human psychopharmacology Hum. Psychopharmacol Clin Exp 2008;23: 707-713 indicate that the effects of risperidone on the noradrenergic system as well as on the serotonergic system might be related to its efficacy in treating negative symptoms of schizophrenia (Yoshimura et al, 2000a(Yoshimura et al, , 2000b and mood disorder (Yoshimura et al, 2006). Taken together, the above results show that the effects of risperidone on three monoaminergic systems (dopamine, serotonin, noradrenaline) are associated with its clinical efficacy for schizophrenia and mood disorder.…”

“…We have reported that risperidone is effective for treating the acute phase of schizophrenia with few extrapyramidal side effects (Yoshimura et al, 2003. Furthermore, we have reported that risperidone is also effective in treating negative symptoms of chronic schizophrenic patients (Yoshimura et al, 2000a). In negative schizophrenic symptomatology and in mood disorders, a disturbance of the serotonergic system has been shown to be of relevance.…”