Disease relevance of Lullan

• Neuroleptic malignant syndrome related to a switch to perospirone and anticholinergic withdrawal [1].
• We report that perospirone may have had positive effects on the obesity of three patients with schizophrenia and on the fasting blood sugar (FBS) and HbA1C of two of them who had type 2 diabetes mellitus [2].
• Future studies would be valuable to elucidate the utility of perospirone for the treatment of involuntary movements and psychiatric symptoms in HD [3].

Psychiatry related information on Lullan

• Effective treatment of coprophagia in a patient with schizophrenia with the novel atypical antipsychotic drug perospirone [4].
• Efficacy of perospirone in the management of aggressive behavior associated with dementia [5].
• Perospirone in treatment of Huntington's disease: A first case report [3].
• Efficacy of carbamazepine against neuroleptic-induced akathisia in treatment with perospirone: case series [6].
• The fact that perospirone antagonizes D(2) receptors could explain its effects on the hyperkinetic syndrome, while its agonistic effects on 5-HT(1A) receptors may explain the amelioration of psychiatric symptoms (fear and anxiety) in this patient [3].

High impact information on Lullan

• The present study suggests that CYP3A4 is significantly involved in metabolism of perospirone in humans [7].
• Perospirone is an atypical antipsychotic agent originated and clinically used in Japan. Based on an in vitro study, it is reported that perospirone is mainly metabolized to ID-15036 by cytochrome P450 (CYP) 3A4 [7].
• Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone [7].
• Plasma concentrations of perospirone, hydroxyperospirone, and prolactin were monitored just before and up to 12 hours after the dosing [8].
• Perospirone is a novel atypical antipsychotic with a unique combination of 5-HT1A receptor agonism as well as 5-HT2A and D2 receptor antagonism [9].

Chemical compound and disease context of Lullan

• We report on a patient with HD, whose involuntary movements and psychiatric symptoms were clinically improved with perospirone, a second-generation antipsychotic agent with antagonistic effects on serotonin 5-HT(2A) and dopamine D(2) (D(2)) receptors, as well as a unique agonistic effect on serotonin 5-HT(1A) (5-HT(1A)) receptors [3].
• We examined the anxiolytic potential of perospirone, a novel serotonin-2 and dopamine-2 antagonist (SDA)-type antipsychotic agent, and compared its effects with those of the standard anxiolytic diazepam and the conventional antipsychotic haloperidol by using conditioned defensive burying (CDB) and social interaction (SI) tests in rats [10].

Biological context of Lullan

• There were no differences in dose-normalized Css(max) or AUC (0-12) perospirone and hydroxyperospirone between 16 mg/day and 32 mg/day of perospirone [8].
• 1. The regional distribution and pharmacological property of binding sites for perospirone, an atypical neuroleptic, in rat brain were examined by an in vitro binding assay [11].
• Applications of perospirone at the concentration between 10(-)(9) and 10(-)(5) M hyperpolarized the membrane potential and inhibited spontaneous action potentials of the DR neurons in a concentration-dependent manner [12].

Anatomical context of Lullan

• Effects of perospirone, a novel antipsychotic agent, on the dopaminergic neurons in the rat ventral tegmental area [13].
• Effects of perospirone, a novel 5-HT2 and D2 receptor antagonist, on Fos protein expression in the rat forebrain [14].
• Thus, the metabolism of perospirone and concomitantly administered drugs did not demonstrate any marked mutual inhibition in the human liver microsomes [15].
• In vitro metabolism of perospirone was examined with rat, monkey and human liver S9, human liver microsomes and yeast microsomes expressing human P450, using 14C labeled perospirone [16].

Associations of Lullan with other chemical compounds

• Pretreatment with a selective 5-HT1A receptor antagonist, WAY 100635, suppressed the increase in dopamine levels induced by the administration of perospirone and fluoxetine to 330% of the baseline value [9].
• Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine D1 receptor-mediated vacuous chewing movement in rats: a role of 5-HT2 receptor blocking activity [17].
• On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) significantly decreased 5-HT2A receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect [18].
• Perospirone is a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist which originated in Japan. It has been shown that perospirone is metabolized to ID-15036 mainly by CYP3A4 based on an in vitro study [19].
• In vitro metabolism studies were conducted to assess drug-drug interactions between perospirone, an antipsychotic agent, and concomitantly administered drugs--biperiden, flunitrazepam, haloperidol, and diazepam--using human liver microsomes [15].

Gene context of Lullan

• Quinidine (a specific inhibitor of CYP2D6) did not markedly affect the metabolism of perospirone, whereas quercetin (an inhibitor of CYP2C8) and ketoconazole (an inhibitor of CYP3A4) caused a decrease in the metabolism with human liver microsomes in a concentration dependent fashion [20].
• The distinct cognitive enhancement profile of perospirone may be attributable to its partial 5-HT1A agonist action [21].
• The change in P300 amplitude following a switch to perospirone correlated significantly with the improvement of general psychopathology symptoms, as well as with the change in scores on items of delusions, hallucinatory behavior, emotional withdrawal, depression, poor attention, and disturbance of volition [22].
• We studied the effects of perospirone (SM-9018), a novel serotonin-2 (5-HT2) and dopamine-2 (D2) receptor antagonist (SDA), on conditioned fear stress (CFS)-induced freezing behavior in rats and compared its actions with those of other antipsychotics [23].
• Switching to equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in indices of verbal memory organization of the Auditory Verbal Learning Test. Negative symptoms and extrapyramidal side effects were also ameliorated after switching to perospirone [21].

Analytical, diagnostic and therapeutic context of Lullan

• Although there were few cases in which psychotropic medication was effective against coprophagia, we encountered a patient with schizophrenia in whom coprophagia rapidly disappeared after treatment with perospirone, a novel atypical antipsychotic drug of the serotonin-dopamine antagonist (SDA) type [4].
• Plasma concentrations of perospirone and ID-15036 up to 10 hours after perospirone dosing were measured by high-performance liquid chromatography (HPLC) [7].
• A simple and sensitive column-switching high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the quantification of perospirone, a serotonin and dopamine antagonist, and its metabolite ID-15036 in human plasma [24].

References