Anodic behavior of aripiprazole(ARP) was studied using electrochemical methods.Charge transfer,diffusion and surface coverage coefcients of adsorbed molecules and the number of electrons transferred in electrode mecha...Anodic behavior of aripiprazole(ARP) was studied using electrochemical methods.Charge transfer,diffusion and surface coverage coefcients of adsorbed molecules and the number of electrons transferred in electrode mechanisms were calculated for quasi-reversible and adsorp-tion-controlled electrochemical oxidation of ARP at 1.15 V versus Ag/AgCl at pH 4.0 in Britton-Robinson buffer(BR) on glassy carbon electrode.Voltammetric methods for direct determination of ARP in pharmaceutical dosage forms and biological samples were developed.Linearity range is found as from 11.4 μM(5.11 mg/L) to 157 μM(70.41 mg/L) without stripping mode and it is found as from 0.221 μM(0.10 mg/L) to 13.6 μM(6.10 mg/L) with stripping mode.Limit of detection(LOD) was found to be 0.11 μM(0.05 mg/L) in stripping voltammetry.Methods were successfully applied to assay the drug in tablets,human serum and human urine with good recoveries between 95.0% and 104.6% with relative standard deviation less than 10%.展开更多
Objectives: To elucidate the pharmacological profile of aripiprazole, we examined its ameliorating effect on the methamphetamine-induced disruption of latent inhibition (LI) in rats. Method: The effect was measured us...Objectives: To elucidate the pharmacological profile of aripiprazole, we examined its ameliorating effect on the methamphetamine-induced disruption of latent inhibition (LI) in rats. Method: The effect was measured using a conditioned emotional response procedure. The conditioned stimulus was a tone (2.8 kHz, 90 dB), and the unconditioned stimulus was a mild foot shock delivered through a floor grid. The conditioning procedure was repeated five times. Results: Methamphetamine-induced (1.0 mg/kg, i.p.) disruption of LI was ameliorated by the administration of haloperidol (0.2 mg/kg, i.p.) and by a moderate dose of aripiprazole (0.3 mg/kg, i.p.) but not by a lower or higher dose (0.1 or 3.0 mg/kg, i.p.) of aripiprazole. However, immunohistochemical examination showed increased levels of c-Fos expression in the shell of the nucleus accumbens after the administration of haloperidol (0.2 mg/kg, i.p.) but not of aripiprazole (0.3 mg/kg, i.p.). Conclusions: It is suggested that aripiprazole has an ameliorating effect on methamphetamine-induced disruption of latent inhibition within only a marginal therapeutic window.展开更多
Objective:To observe the effect of aripiprazole and olanzapine on the cognitive function in patients with schizophrenia in order to provide a reference evidence for the clinical medication.Methods:A total of 60 patien...Objective:To observe the effect of aripiprazole and olanzapine on the cognitive function in patients with schizophrenia in order to provide a reference evidence for the clinical medication.Methods:A total of 60 patients with schizophrenia who were admitted in our hospital were included in the study and randomized into the treatment 1 group and treatment 2 group.The patients in the two groups were given aripiprazole and olanzapine,respectively.PANSS,WCST,DS,IGT,and EIRT were used to evaluate the disease condition and cognitive function before and after treatment in the two groups.Results:Comparision of PANSS scores and other various scores before treatment between the two groups was not significantly different(P>0.05);however,PANSS scores and other various scores after treatment were significantly reduced(P<0.05).Comparision of PANSS scores and other various scores after treatment between the two groups was not significantly different(P>0.05).DS,WCST,and IGT scores before treatment between the two groups was comparable(P>0.05),and those scores after treatment were significantly elevated(P<0.05).DS score after treatment in the treatment 2 group was significantly higher than that in the treatment 1 group(P<0.05).Comparison of WCST and IGT scores after treatment between the two groups was not significantly different(P>0.05).The four cognition scores of happiness,fear,anger,and disgust after treatment in the treatment 1 group were significantly elevated(P<0.05),while the cognition of happiness and sadness after treatment in the treatment 2 group was significantly elevated when compared with before treatment(P<0.05).The comparison of various scores before and after treatment between the two groups was not significantly different(P>0.05).Conclusions:Aripiprazole and olanzapine can improve the clinical symptoms and partial cognitive function in patients with schizophrenia,while aripiprazole can make a better effect on the work and memory.展开更多
Aripiprazole, a third-generation antipsychotic, has been considered to have a high safety profile and rare withdrawal symptoms. We reported the case of a schizophrenic patient with a significant obsession, who was tre...Aripiprazole, a third-generation antipsychotic, has been considered to have a high safety profile and rare withdrawal symptoms. We reported the case of a schizophrenic patient with a significant obsession, who was treated with a high dosage of aripiprazole and fluoxetine. Generalized tonic-clonic seizure occurred two days after abruptly stopping these two medications. Gradually tapering aripiprazole is suggested in clinical practice, especially when using a high dosage.展开更多
The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed wi...The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.展开更多
Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports tha...Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.展开更多
Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability a...Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.展开更多
Drug metabolism is an important issue in drug discovery. Understanding how a drug is metabolized in the body will provide helpful information for lead optimization. Cytochrome P450 2D6 （CYP2D6） is a key enzyme for d...Drug metabolism is an important issue in drug discovery. Understanding how a drug is metabolized in the body will provide helpful information for lead optimization. Cytochrome P450 2D6 （CYP2D6） is a key enzyme for drug metabolism and responsible for the metabolism of about one third marketed drugs. Aripiprazole is an atypical an- tipsychotic and metabolized by CYP2D6 to its hydroxylated form. In this study, a series of computational methods were performed to understand how CYP2D6 accomplishes the 4-hydroxylation of aripiprazole. Molecular docking and molecular dynamics simulations were first performed to prepare the initial conformations for QM/MM calcula- tions. The results revealed two possible conformations for the drug-CYP2D6 complex. The ONIOM method for QM/MM calculations was then carried out to show detailed reaction pathways for the CYP2D6-catalyzed aripipra- zole hydroxylation reaction, which demonstrated that the dominant reactive channel was electrophilic and involved an initial attack on the n-system of the dichlorophenyl group of aripiprazole to produce cation δ-complex. Further- more, the product complex for each conformation was thermodynamically stable, which is in good agreement with previous reports.展开更多
Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naTve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitiv...Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naTve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.展开更多
Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule...Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule drug with aripiprazole as the active pharmaceutical ingredient） oral solution and die- thylenetriaminepentaacetic acid （DTPA） in Yervoy （a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient） intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions （Cu2＋, Fe3＋） which generate highly stable metallocom- plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in- volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de- termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids （APCAs） including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.展开更多
Schizophrenia is a group of the most common types of mental illness.Commonly used antischizophrenia drugs all increase mortality to some extent.The increased risk of death in older individuals and patients with dement...Schizophrenia is a group of the most common types of mental illness.Commonly used antischizophrenia drugs all increase mortality to some extent.The increased risk of death in older individuals and patients with dementia using atypical antips-ychotics may be due to myocardial damage,increased mobility and increased risk of stroke.展开更多
Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidati...Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury,leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient.The mononuclear cells layer was resuspended in cell culture medium.Oxidative stress was induced with hydrogen peroxide in cultured leukocytes.Four days later,leukocytes were treated with aripiprazole,haloperidol or clozapine for 7 days.Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23%and 20%in peripheral blood mononuclear cells after acute oxidative stress injury.These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress.The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of Sao Paulo(FMUSP/CAAE approval No.52622616.8.0000.0065).展开更多
基金Scientific Research Unit of Ankara University forfinancial support with Grant number:11B4240005
文摘Anodic behavior of aripiprazole(ARP) was studied using electrochemical methods.Charge transfer,diffusion and surface coverage coefcients of adsorbed molecules and the number of electrons transferred in electrode mechanisms were calculated for quasi-reversible and adsorp-tion-controlled electrochemical oxidation of ARP at 1.15 V versus Ag/AgCl at pH 4.0 in Britton-Robinson buffer(BR) on glassy carbon electrode.Voltammetric methods for direct determination of ARP in pharmaceutical dosage forms and biological samples were developed.Linearity range is found as from 11.4 μM(5.11 mg/L) to 157 μM(70.41 mg/L) without stripping mode and it is found as from 0.221 μM(0.10 mg/L) to 13.6 μM(6.10 mg/L) with stripping mode.Limit of detection(LOD) was found to be 0.11 μM(0.05 mg/L) in stripping voltammetry.Methods were successfully applied to assay the drug in tablets,human serum and human urine with good recoveries between 95.0% and 104.6% with relative standard deviation less than 10%.
文摘Objectives: To elucidate the pharmacological profile of aripiprazole, we examined its ameliorating effect on the methamphetamine-induced disruption of latent inhibition (LI) in rats. Method: The effect was measured using a conditioned emotional response procedure. The conditioned stimulus was a tone (2.8 kHz, 90 dB), and the unconditioned stimulus was a mild foot shock delivered through a floor grid. The conditioning procedure was repeated five times. Results: Methamphetamine-induced (1.0 mg/kg, i.p.) disruption of LI was ameliorated by the administration of haloperidol (0.2 mg/kg, i.p.) and by a moderate dose of aripiprazole (0.3 mg/kg, i.p.) but not by a lower or higher dose (0.1 or 3.0 mg/kg, i.p.) of aripiprazole. However, immunohistochemical examination showed increased levels of c-Fos expression in the shell of the nucleus accumbens after the administration of haloperidol (0.2 mg/kg, i.p.) but not of aripiprazole (0.3 mg/kg, i.p.). Conclusions: It is suggested that aripiprazole has an ameliorating effect on methamphetamine-induced disruption of latent inhibition within only a marginal therapeutic window.
基金Science and technology research and development program of Hebei province(No.1221068D).
文摘Objective:To observe the effect of aripiprazole and olanzapine on the cognitive function in patients with schizophrenia in order to provide a reference evidence for the clinical medication.Methods:A total of 60 patients with schizophrenia who were admitted in our hospital were included in the study and randomized into the treatment 1 group and treatment 2 group.The patients in the two groups were given aripiprazole and olanzapine,respectively.PANSS,WCST,DS,IGT,and EIRT were used to evaluate the disease condition and cognitive function before and after treatment in the two groups.Results:Comparision of PANSS scores and other various scores before treatment between the two groups was not significantly different(P>0.05);however,PANSS scores and other various scores after treatment were significantly reduced(P<0.05).Comparision of PANSS scores and other various scores after treatment between the two groups was not significantly different(P>0.05).DS,WCST,and IGT scores before treatment between the two groups was comparable(P>0.05),and those scores after treatment were significantly elevated(P<0.05).DS score after treatment in the treatment 2 group was significantly higher than that in the treatment 1 group(P<0.05).Comparison of WCST and IGT scores after treatment between the two groups was not significantly different(P>0.05).The four cognition scores of happiness,fear,anger,and disgust after treatment in the treatment 1 group were significantly elevated(P<0.05),while the cognition of happiness and sadness after treatment in the treatment 2 group was significantly elevated when compared with before treatment(P<0.05).The comparison of various scores before and after treatment between the two groups was not significantly different(P>0.05).Conclusions:Aripiprazole and olanzapine can improve the clinical symptoms and partial cognitive function in patients with schizophrenia,while aripiprazole can make a better effect on the work and memory.
文摘Aripiprazole, a third-generation antipsychotic, has been considered to have a high safety profile and rare withdrawal symptoms. We reported the case of a schizophrenic patient with a significant obsession, who was treated with a high dosage of aripiprazole and fluoxetine. Generalized tonic-clonic seizure occurred two days after abruptly stopping these two medications. Gradually tapering aripiprazole is suggested in clinical practice, especially when using a high dosage.
文摘The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.
基金supported by Chongqing basic research and frontier exploration project(cstc2022ycjh-bgzxm0119,China)。
文摘Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
基金supported by the National Natural Science Foundation of China(NSFC,81971734,32071323,32271410),the Program for Innovative Research Team in Science and Technology in Fujian Province.
文摘Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.
基金the China Postdoctoral Science Foundation，Shanghai Committee of Science and Technology，National Natural Science Foundation of China，Innovation Program of Shanghai Municipal Education Commission
文摘Drug metabolism is an important issue in drug discovery. Understanding how a drug is metabolized in the body will provide helpful information for lead optimization. Cytochrome P450 2D6 （CYP2D6） is a key enzyme for drug metabolism and responsible for the metabolism of about one third marketed drugs. Aripiprazole is an atypical an- tipsychotic and metabolized by CYP2D6 to its hydroxylated form. In this study, a series of computational methods were performed to understand how CYP2D6 accomplishes the 4-hydroxylation of aripiprazole. Molecular docking and molecular dynamics simulations were first performed to prepare the initial conformations for QM/MM calcula- tions. The results revealed two possible conformations for the drug-CYP2D6 complex. The ONIOM method for QM/MM calculations was then carried out to show detailed reaction pathways for the CYP2D6-catalyzed aripipra- zole hydroxylation reaction, which demonstrated that the dominant reactive channel was electrophilic and involved an initial attack on the n-system of the dichlorophenyl group of aripiprazole to produce cation δ-complex. Further- more, the product complex for each conformation was thermodynamically stable, which is in good agreement with previous reports.
基金sponsored by the National Key Project of Scientific and Technical Supporting Programs Funded by the Ministry of Science & Technology of China,No.2007BAI17B04the National Natural Science Foundation of China,No.30900485the National R&D Special Fund for Health Professions,No.201002003
文摘Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naTve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.
文摘Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule drug with aripiprazole as the active pharmaceutical ingredient） oral solution and die- thylenetriaminepentaacetic acid （DTPA） in Yervoy （a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient） intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions （Cu2＋, Fe3＋） which generate highly stable metallocom- plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in- volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de- termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids （APCAs） including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.
基金Supported by Curriculum Reform Project of Taizhou University in 2021, No. xkg2021087
文摘Schizophrenia is a group of the most common types of mental illness.Commonly used antischizophrenia drugs all increase mortality to some extent.The increased risk of death in older individuals and patients with dementia using atypical antips-ychotics may be due to myocardial damage,increased mobility and increased risk of stroke.
基金supported by grants from FAPESP(Fundacao de AmparoàPesquisa de Sao Paulo,Grant no 2016/01302-9 and 2014/27129-6)CAPES(Coordenacao de Aperfeicoamento de Pessoal de Nível Superior)88887.463672/2019-00。
文摘Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury,leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient.The mononuclear cells layer was resuspended in cell culture medium.Oxidative stress was induced with hydrogen peroxide in cultured leukocytes.Four days later,leukocytes were treated with aripiprazole,haloperidol or clozapine for 7 days.Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23%and 20%in peripheral blood mononuclear cells after acute oxidative stress injury.These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress.The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of Sao Paulo(FMUSP/CAAE approval No.52622616.8.0000.0065).
