• Title/Summary/Keyword: Risperidone

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Risperidone(R 64766)의 제 1상 임상 연구: 일회 경구투여에 따른 약동학 및 내약성 검토

  • 신상구;이경훈;장인진;신재국;정원석
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1992.05a
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    • pp.56-56
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    • 1992
  • Risperidone은 D$_2$-수용체와 HT$_2$-수용체 차단효과를 동시에 지녀, 차세대 항정신분열증 치료제로의 가능성을 보이고 있는 약물이다. 그러나 risperidone의 주대사가 CYPIID1에 의할 가능성이 시사되고 있다. 본 연구에서는 향후 항정신병 치료제의 임상 제 1상 연구의 적정 모형 검토를 위해 risperidone율 모델 약물로 체내 약물의 동태, 내약성 및 약물 유전학적 특성등을 검토하였다. CYPIID1의 대사능을 검정한 12명의 정상 성인(11명: extensive metabolizer, 1명: poor metabolizer)을 대상으로 risperidone 투여 시험(placebo, 1, 2 mg)을 무작위 단일맹검 교차시험으로 시행하였다. 투약후 72시간까지 경시적으로 혈액, 뇨 채취 및 ECG lead II, 혈압/맥박의 변동 등을 측정하고, visual analog scale에 의해 중추신경계 주관적 증상들을 관찰 하였다. 혈장 risperidone 및 그 활성형대사물 9-OH risperidone 및 prolactin 농도는 radioimmunoassay법으로 측정하였다.

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Risperidone Monotherapy in Children and Adolescents with Autism Spectrum Disorders : A Naturalistic Study

  • Won, Eun-Kyung;Park, Jin-Park;Lee, Young-Ryul;Nam, Yoon-Young;Min, He-Ji;Kim, Yeni
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.26 no.4
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    • pp.273-278
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    • 2015
  • Objectives : We retrospectively investigated the efficacy and tolerability of risperidone monotherapy in subjects with autism spectrum disorder (ASD). In addition, we did mixed effect model analysis of the effects of risperidone in patients with ASDs naturalistically treated in a routine clinical setting to determine whether the clinical effects were maintained and the side effects were tolerable. Methods : This retrospective study assessed children and adolescents with ASD, who were on risperidone monotherapy from July 2010 to July 2011 at the Child and Adolescent ASD Clinic at Seoul National Hospital. Outcome measures included the Clinical Global Impression-Severity of Illness (CGI-S) and the CGI-Improvement (CGI-I) scales along with other clinical indices: dosage, target symptoms, and side effects. Results : The mean dose of risperidone in 47 children and adolescents with ASD (40 males, 7 females; age range 5-19 years) who were on risperidone monotherapy was $1.6{\pm}0.8mg/day$, and the mean duration of the treatment period was $20.2{\pm}17.3months$. Aggressive behavior, stereotypic behavior, irritability, and self-injurious behavior were the most frequent target symptoms of risperidone. The most common side effects were weight gain followed by somnolence and extrapyramidal symptoms. In a mixed effects model analysis of CGI-I scores, the mean CGI-I score at the 1 month follow-up was significantly different from the mean CGI-I score of the 3-month follow-up (p=.046), and the CGI-I scores were equally maintained over 3 to 48 months [F(6, 28.9)=4.393, p=.003]. Of the 47 patients, 33 patients (70.2%) were identified as the response group, showing an end point CGI-I rating of 3 or under and having continued risperidone treatment for at least 6 months. The baseline CGI-S score showed significant association with clinical response to risperidone (p=.005), the mean baseline CGI-S was higher in the response group compared to the non-response group. Conclusion : In this study, clinical improvement of risperidone stabilized around 3 months and was equally maintained up to 48 months with tolerable side effects, supporting maintenance of risperidone treatment in children and adolescents with ASDs.

BIOEQUIVALENCE EVALUATION OF RISPERIDONE 2 MG TABLETS IN HEALTHY MALE KOREAN VOLUNTEERS

  • Cho, Hea-Young;Kang, Hyun-Ah;Lee, Yong-Bok
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.309.1-309.1
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    • 2003
  • The purposes of this study were to evaluate bioequivalence (BE) using In-transformed pharmacokinetic parameters obtained from two risperidone products and to develop the analytical methods for the quantitative determination of risperidone in human serum. In addition, the in vitro dissolution profiles of the two risperidone products in various dissolution media: pH 1.2, 4.0, 6.8 and water (KP VII Apparatus II method) were assesed. (omitted)

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Effect of Acute and Chronic Treatment with Risperidone on the Serotonin and Dopamine Receptors in the Rat Brain (Risperidone의 급성 및 만성 투여가 흰쥐 뇌의 Serotonin과 Dopamine 수용체에 미치는 영향)

  • Choi, Yun-Young;Son, Hye-Kyung;Kim, Chang-Yoon;Lee, Chul;Lee, Hee-Kyung;Moon, Dae-Hyuk
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.1
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    • pp.9-18
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    • 1997
  • The therapeutic efficacy of antipsychotic drugs is generally attributed to their ability to block dopamine $D_2$ receptors. Classical $D_2$ antagonists are not effective to treat negative symptoms and produce extrapyramidal side effects On the other hand, atypical antipsychotic agents ameliorate negative symptoms without producing extra-pyramidal side effects, and it is reported to be associated with blockade of serotonin $5-HT_2$ receptors. The purpose of this study was to evaluate the effect of risperidone on neuroreceptors in the rat brain by Quantitative autoradiography method. In acute treatment group, risperidone was injected into Peritoneal cavity of male Wistar rats with dose of 0, 0.1, 0.25, 0.5, 1.0 and 2.0mg/kg in each group(5/group), and they were decapitated after 2 hours. In chronic treatment group, risperidone was injected with dose of 0, 0.1, and 1mg/kg(I.P.) for 21 days and decapitated after 24 hours following last treatment. The effect of risperodone on the binding of [$^3H$]spiperone to $5-HT_2$ and $D_2$ receptors were analysed in 4 discrete regions of the striatum, nucleus accumbens, and frontal cortex by quantitative autoradiography Acute treatment with risperidone reduced cortical $5-HT_2$ specific [$^3H$]spiperone binding to 32% of vehicle-treated control. Subcortical $5-HT_2$ specific [$^3H$]spiperone binding was not affected at all dose groups whereas a significant reduction (57%) in $D_2$ specific [$^3H$]spiperone binding was observed in risperidone treated group at doses of 1-2mg/kg. Chronic treatment with risperidone produced a decrease in the maximal number of cortical $5-HT_2$ receptors to 51% and 46% of control in 0.1mg/kg & 1mg/kg treated group respectively. In conclusion, risperidone is a cortical serotonin receptor antagonist with relatively weak antagonistic action on dopamine receptors. These effects oil neuroreceptors may explain the therapeutic effect of risperidone as a atypical antipsychotic agents.

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The Cardiovascular Effect of Risperidone (리스페리돈이 심혈관계에 미치는 영향)

  • Choi, Se-Jin;Cheon, Jin-Sook;Choi, Young-Tai
    • Korean Journal of Biological Psychiatry
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    • v.7 no.2
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    • pp.191-197
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    • 2000
  • Objectives : Risperidone is a new antipsychotic drug developed to overcome the therapeutic limitation of conventional antipsychotics. It responses to negative as well as positive symptoms by blocking both dopaminergic and serotonergic receptors, causing no significant side effects such as agranulocytosis and seizure. It is, however, not known whether it induces any serious cardiovascular side effects as evoked by other conventional antipsychotic drugs. The aims of this study were to evaluate the effect of risperidone on cardiovascular function, and to discuss the factors affecting the cardiovascular function. Methods : For 42 patients(22 males and 20 females) diagnosed as schizophrenia, schizophreniform disorder or schizoaffective disorder according to the DSM-IV classification, the cardiovascular fuctions such as heart rate, systolic and diastolic blood pressure, PR interval, QRS interval and QT interval were successively checked before and after 2 weeks and 4 weeks risperidone administration. Furthermore, variables such as body weight, Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression(CGI), Extrapyramidal Symptom Rating Scale(ESRS), Anticholinergic Rating Scale(ARS), serum cholesterol level, serum triglyceride level, serum high-density-lipoprotein level, serum WBC, serum Hb, serum platelet level, prothrombin time and partial thromboplastin time were also analyzed before and after 2 weeks and 4 weeks risperidone administration. Results : 1) Risperidone treatment resulted in a significantly decreased heart rate and increased QT interval after 4 weeks administration(p<0.005 respectively). 2) The scores of BPRS and CGI were significantly decreased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). The scores of ESRS and ASRS were significantly increased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). 3) There were positive correlations between heart rate after 4 weeks and total dose(P<0.05). Blood pressure was significantly(p<0.05) correlated with sex(higher in male) and significantly(p<0.05) positive correlated with body weight. QT interval was significantly(p<0.05) correlated with sex(longer in female) and smoking history(shorter in smokers). Conclusions : Risperidone could induce significant change in heart rate and Q-T interval. Therefore, the cardiovascular safety for risperidone should be reconsidered according to the duration and dosage increase.

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An Efficient Synthesis of Risperidone via Stille Reaction: Antipsychotic, $5-HT_2$, and $Dopamine-D_2-Antagonist$

  • Kim Dong-myung;Kang Min-Seok;Kim Jeong Sook;Jeong Jin-Hyun
    • Archives of Pharmacal Research
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    • v.28 no.9
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    • pp.1019-1022
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    • 2005
  • Risperidone has been reported to have neuroleptic activity. In this study, risperidone was synthesized using a new method involving a stille reaction, in which 2-methyl-3-vinyl-6,7,8,9-tet­rahydropyrido[1 ,2-a]pyrimidin-4-one was synthesized (5). The chemical synthesis process was found to be simple and produced risperidone in a high yield. In addition, can be easily scaled up for large scale synthesis.

Switch to Olanzapine from Clozapine or Risperidone and 12-months Follow Up (Clozapine과 Risperidone에서 Olanzapine으로 교체 연구 : 12개월 추적연구)

  • Cho, Bang Hyun;Jung, In Kwa;Paik, Jong Woo
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.140-146
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    • 2001
  • In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

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The Effect of Risperidone on Serum Prolactin Concentrations (Risperidone이 혈청 Prolactin 농도에 미치는 영향)

  • Cheon, Jin-Sook;Cho, Woong;Oh, Byoung-Hoon
    • Korean Journal of Biological Psychiatry
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    • v.5 no.2
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    • pp.253-262
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    • 1998
  • Objectives : Risperidone, an atypical antipsychitics which blocks both dopaminergic and serotonergic receptors, have a good response to the negative symptoms as well as positive symptoms, and improve cognitive dysfunction of schizophrenic patients. Furthermore, it has few extrapyramidal side effects and tardive dyskinesia. Although it had been reported that the atypical antipsychotics have less effect on prolactin(PRL) than the classical antipsychotics, we could experience PRL-associated symptoms such as amenorrhea, galactorrhea and hyperprolactinemia in practice. Therefore, we tried to identify the sex differences of risperidone-induced hyperprolactinemia, to evaluate factors affecting PRL levels, and to know the association between cognitive disorders and PRL. Methods : The baseline levels of PRL and TSH prior to risperidone administration were measured by enzyme immunoassay method for 50 patients(25 ma-les and 25 females) admitted with schizophrenia, schizoaffective disorder or schizophreniform disorder according to the DSM-IV classification, and the measurements of PRL were repeated on the 2nd and the 4th wks of risperidone administration. Concomitantly, the severity of psychotic symptoms using CGI, BPRS and PANSS, and the cognitive dysfunction using PANSS-CF were assessed prior to, on the 2nd and the 4th wks of risperidone administration. The PRL and TSH levels of 54 healthy controls(29 males and 25 females) who had no medical, neurological and psychiatric illnesses were also evaluated. Furthermore, the correlation with the psychiatric diagnosis, education, age, sex, duration of illnesses, risperidone dosage, duration of risperdone administration, TSH concentration, cognitive function, severity of psychotic symptoms were also identified. Results : 1) The baseline PRL levels of female schizophrenics($74.3{\pm}49.6ng/ml$) were significantly(p<0.005) higher than those of males($36.3{\pm}24.6ng/ml$), which were significantly(p<0.0001 respectively) higher than those of controls(females $16.9{\pm}6.1ng/ml$, males $13.3{\pm}4.9ng/ml$). The PRL levels measured on the 2nd wks(females $133.7{\pm}47.8ng/ml$, males $56.9{\pm}23.6ng/ml$) and on the 4th wks(females $146.1{\pm}45.9ng/ml$, males $70.0{\pm}31.5ng/ml$) after risperidone administration were significantly(p<0.0001 respectively) higher in females. The mean dosages of risperidone on the 2nd wks were $3.8{\pm}1.7mg$(2-6mg) for the females and $4.0{\pm}1.6mg$(2-6mg) for the males, and on the 4th wks were $4.5{\pm}2.1mg$(2-8mg) for the females and $5.4{\pm}2.2mg$(2-8mg) for the males. 2) The rise of PRL levels were positively correlated with increased risperidone dosage in males(${\gamma}$=0.307 on the 2nd wks and ${\gamma}$=0.280 on the 4th wks), while they were not correlated with dosages in females. For the females, the PRL levels were negatively correlated(${\gamma}$=-0.320) with decrease of TSH concentration. The baseline PRL levels were not correlated with age, education, duration of illnesses, psychopathology, cognitive disorders in both males and females, while it was negatively correlated with TSH levels only in females(${\gamma}$=-0.320). 3) The cognitive dysfunction was not correlated with PRL levels in males, while PANSS-CF scores were negatively correlated with PRL levels(${\gamma}$=-0.220 on the 2nd wks and ${\gamma}$=-0.366 on the 4th wks) in females. The psychopathology was positively correlated with cognitive dysfunction in both males and females. Therefore, the risperidone-induced cognitive improvement seemed to be correlated with improvement of psychopathology in both males and females, and with increase in PRL levels only in females. Conclusions : The fact that the serum PRL levels of schizophrenics were higher than those of controls, especially in females suggested that it could be related with risperidone dosage in males and with primary pathological process in females. The risperidone-associated cognitive improvement seemed to be related with general improvement of psychopathology as well as the rise of PRL levels especially in females. The facts that the effect of risperidoneinduced hyperprolactinemia and the cognitive function were more in females suggested that somewhat different mechanisms could be exerted on them.

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Dopamine Transporter Density Assessed with $[^{123}I]IPT$ SPECT Before and After Risperidone Treatment in Children with Tourette's Disorder (뚜렛 장애 아동에서 Risperidone 치료 전후 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 도파민 운반체 밀도)

  • Kim, Tae-Hoon;Ryu, Won-Gee;Park, Se-Young;Chi, Dae-Yoon;Choi, Tae-Hyun;Lee, Kyung-Yul;Cheon, Keun-Ah;Yun, Mi-Jin;Kim, Jai-Keun;Lee, Jong-Doo;Ryu, Young-Hoon
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.1
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    • pp.41-51
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    • 2004
  • PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

A Case of Transient Psychosis Suspected to be Induced by Arachnoid Cyst, Which was Responsive to Risperidone (거미낭으로 일과성 정신병 유발이 의심되고 리스페리돈 치료에 효과적이었던 증례)

  • Bahk, Won-Myong;Pae, Chi-Un;Jun, Taeyoun;Kim, Kwang-Soo;Lew, Tae-Yul
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.153-155
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    • 2001
  • There had been few reports of arachnoid cyst accompanying psychiatric disturbance and no report treated with low-dose risperidone administration. We report a patient, developed first-transient psychotic episode considered to be provoked by an arachnoid cyst, responsive to risperidone, which was found in the middle cranial fossa as follows. A 57-year-old man was admitted by suddenly developed headache, auditory hallucination, delusion of persecution and, an arachnoid cyst in the anteromedial aspect of middle cranial fossa was found on MRI after admission. The psychotic episode was first to him and he was also negative to other clinical evaluation including endocrine abnormality, his psychotic symtom was suspected to be induced by arachnoid cyst and was well controlled to low-dose risperidone administration. He left hospital free from psychotic symptoms on 14 hospital days.

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