International Journal of Neuropsychopharmacology最新文献

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Quantitative Evaluation of Multiple Treatment Regimens for Treatment-Resistant Depression.
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2025-01-25 DOI: 10.1093/ijnp/pyaf007
Yulin Feng, Yinghua Lv, Juan Yang, Ling Xu, Junchao Chen, Jihan Huang, Jiyuan Ren, Qingshan Zheng, Lujin Li
{"title":"Quantitative Evaluation of Multiple Treatment Regimens for Treatment-Resistant Depression.","authors":"Yulin Feng, Yinghua Lv, Juan Yang, Ling Xu, Junchao Chen, Jihan Huang, Jiyuan Ren, Qingshan Zheng, Lujin Li","doi":"10.1093/ijnp/pyaf007","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf007","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to quantitatively evaluate the efficacy and safety of various treatment regimens for treatment-resistant depression (TRD) across oral, intravenous, and intranasal routes to inform clinical guidelines.</p><p><strong>Methods: </strong>A systematic review identified randomized controlled trials on TRD, with efficacy measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS). We developed pharmacodynamic and covariate models for different administration routes, using Monte Carlo simulations to estimate efficacy distribution. Dropout and adverse event-related dropout rates were analyzed via single-arm meta-analysis.</p><p><strong>Results: </strong>Involving 22 studies with 56 treatment arms and 3,059 patients, our findings suggest combination therapies outperform monotherapy, achieving an additional 6.5% reduction in MADRS scores over 12 weeks. The most effective combinations were olanzapine with fluoxetine and quetiapine with SSRIs/SNRIs. Injectable treatments, particularly ayahuasca, produced rapid effects, with a 77% reduction in MADRS scores at 15 days. Intranasal treatments reached efficacy sooner than oral ones, with 28-day efficacy similar to the 12-week efficacy of the olanzapine-fluoxetine combination. Dropout rates due to adverse events were similar across methods (4.5%-5.2%), but total dropouts were highest for oral (17.9%) and lowest for intranasal routes (10.6%). Additionally, there was considerable variation in the incidence of headache, dizziness, and nausea across different administration routes.</p><p><strong>Conclusion: </strong>The quantitative evaluation of 22 TRD treatments illuminates key pharmacodynamic parameters, bolstering the development of clinical guidelines and aiding the design of clinical trials and medical decision-making.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer Disease. 研究 IL-6 和 CXCL8 对阿尔茨海默病神经变性和认知能力下降的影响
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae038
Dongdong Jin, Min Zhang, Lei Shi, Hengfang Liu
{"title":"Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer Disease.","authors":"Dongdong Jin, Min Zhang, Lei Shi, Hengfang Liu","doi":"10.1093/ijnp/pyae038","DOIUrl":"10.1093/ijnp/pyae038","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression.</p><p><strong>Methods: </strong>We utilized Gene Expression Omnibus datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology.</p><p><strong>Results: </strong>The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues.</p><p><strong>Conclusions: </strong>The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer disease.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial. 谷氨酸抑制剂evenamide对治疗性精神分裂症(TRS)患者的治疗作用:一项开放标签、非盲法、随机、国际临床试验的1年最终结果。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae061
Ravi Anand, Alessio Turolla, Giovanni Chinellato, Arjun Roy, Richard D Hartman
{"title":"Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial.","authors":"Ravi Anand, Alessio Turolla, Giovanni Chinellato, Arjun Roy, Richard D Hartman","doi":"10.1093/ijnp/pyae061","DOIUrl":"10.1093/ijnp/pyae061","url":null,"abstract":"<p><p>The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a glutamate modulator, were not associated with any safety abnormalities at all doses (7.5-30 mg bid), with a high retention rate even at 6-month (~85%), and 1-year (~75%), and the absence of psychotic relapses during the 1-year treatment period. Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures (eg, PANSS mean change ~ -20%; CGI-S mean change ~ -1.0). In addition, compared to the results at Week 6, the responder rates generally more than doubled at 1-year (PANSS \"≥20% improvement from baseline\" = ~45%; CGI-S \"2-category of improvement\" = ~25%; CGI-C \"much improved\" = ~40%). These results, rarely replicated in other trials in TRS, support the use of evenamide as an add-on treatment in patients who are not benefiting from their current first- or second-generation antipsychotic medication.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial. 一种新型致幻剂N,N-二甲基色胺/鼠胺配方在健康受试者中的药代动力学和药效学:一项随机对照试验。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyaf001
Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B Quednow, Milan Scheidegger
{"title":"Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.","authors":"Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B Quednow, Milan Scheidegger","doi":"10.1093/ijnp/pyaf001","DOIUrl":"10.1093/ijnp/pyaf001","url":null,"abstract":"<p><strong>Background: </strong>Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.</p><p><strong>Methods: </strong>This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.</p><p><strong>Results: </strong>N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.</p><p><strong>Conclusions: </strong>This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.</p><p><strong>Clinical trial registration number: </strong>Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats. 苍白质P和神经激肽受体在大鼠空间记忆巩固中的作用。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyaf002
Erika Kertes, László Péczely, Tamás Ollmann, Kristóf László, Beáta Berta, Veronika Kállai, Olga Zagorácz, Anita Kovács, Ádám Szabó, Zoltán Karádi, László Lénárd
{"title":"The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats.","authors":"Erika Kertes, László Péczely, Tamás Ollmann, Kristóf László, Beáta Berta, Veronika Kállai, Olga Zagorácz, Anita Kovács, Ádám Szabó, Zoltán Karádi, László Lénárd","doi":"10.1093/ijnp/pyaf002","DOIUrl":"10.1093/ijnp/pyaf002","url":null,"abstract":"<p><strong>Background: </strong>The tachykinin substance P (SP) facilitates learning and memory processes after its central administration. Activation of its different receptive sites, neurokinin-1 receptors (NK1Rs), as well as NK2Rs and NK3Rs, was shown to influence learning and memory. The basal ganglia have been confirmed to play an important role in the control of memory processes and spatial learning mechanisms, and as part of the basal ganglia, the globus pallidus (GP) may also be involved in this regulation. SP-immunoreactive fibers and terminals, as well as NK1Rs and NK3Rs, were shown to be present in the GP.</p><p><strong>Methods: </strong>The present study aimed to examine whether the SP administered into the GP can influence spatial memory consolidation in the Morris water maze (MWM). Therefore, male Wistar rats received a post-trial microinjection of 0.4 µLf 10 ng SP, 100 ng SP, or vehicle solution. The possible involvement of pallidal NK1Rs and NK3Rs in the SP effects was also studied by applying WIN51708 for NK1R antagonism and SR142801 as a selective NK3R antagonist.</p><p><strong>Results: </strong>Our results showed that the lower dose of SP significantly decreased escape latency on the second day compared to control animals, while the higher dose was ineffective. Prior treatment with the NK1R antagonist WIN51708 could not block, while the NK3R antagonist SR142801 inhibited the effects of SP on memory consolidation in the MWM.</p><p><strong>Conclusions: </strong>Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: a randomized, double-blind, placebo-controlled trial. 己酮可可碱辅助利培酮治疗稳定型精神分裂症阴性症状:一项随机、双盲、安慰剂对照试验
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae051
Ahmad Shamabadi, Elham-Sadat Rafiei-Tabatabaei, Kimia Kazemzadeh, Kimia Farahmand, Bita Fallahpour, Mohammad-Reza Khodaei Ardakani, Shahin Akhondzadeh
{"title":"Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: a randomized, double-blind, placebo-controlled trial.","authors":"Ahmad Shamabadi, Elham-Sadat Rafiei-Tabatabaei, Kimia Kazemzadeh, Kimia Farahmand, Bita Fallahpour, Mohammad-Reza Khodaei Ardakani, Shahin Akhondzadeh","doi":"10.1093/ijnp/pyae051","DOIUrl":"10.1093/ijnp/pyae051","url":null,"abstract":"<p><strong>Background: </strong>Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients in whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow-increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia.</p><p><strong>Methods: </strong>Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo every 12 hours for 8 weeks. All patients were clinically stable as they had received risperidone for at least 2 months, which was continued. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Extrapyramidal Symptom Rating Scale, and side effect checklist.</p><p><strong>Results: </strong>The patients' baseline characteristics were comparable between the groups. There was a significant time-treatment interaction effect on PANSS negative subscale scores (ηP2=0.075), with the pentoxifylline group showing significantly greater reductions until weeks 4 (Cohen d = 0.512) and 8 (Cohen d = 0.622). Also, this group showed a significantly better response by week 8. Other PANSS scores, Hamilton Depression Rating Scale scores, Extrapyramidal Symptom Rating Scale scores, and side effect frequencies were comparable between the groups. Pentoxifylline showed a nonsignificant higher remission of 37.1% compared with 14.7% in the placebo group.</p><p><strong>Conclusions: </strong>Pentoxifylline was safely and tolerably beneficial for the primary negative symptoms of chronic schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disrupting heroin-associated memory reconsolidation through actin polymerization inhibition in the nucleus accumbens core. 通过抑制伏隔核的肌动蛋白聚合破坏海洛因相关记忆的再巩固。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae065
Haiting Zhao, Haoyu Li, Li Meng, Peng Du, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao
{"title":"Disrupting heroin-associated memory reconsolidation through actin polymerization inhibition in the nucleus accumbens core.","authors":"Haiting Zhao, Haoyu Li, Li Meng, Peng Du, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao","doi":"10.1093/ijnp/pyae065","DOIUrl":"10.1093/ijnp/pyae065","url":null,"abstract":"<p><strong>Background: </strong>Understanding drug addiction as a disorder of maladaptive learning, where drug-associated or environmental cues trigger drug cravings and seeking, is crucial for developing effective treatments. Actin polymerization, a biochemical process, plays a crucial role in drug-related memory formation, particularly evident in conditioned place preference paradigms involving drugs like morphine and methamphetamine. However, the role of actin polymerization in the reconsolidation of heroin-associated memories remains understudied.</p><p><strong>Methods: </strong>This study employed a rodent model of self-administered heroin to investigate the involvement of actin polymerization in the reconsolidation of heroin-associated memories. Rats underwent ten days of intravenous heroin self-administration paired with conditioned cues. Subsequently, a 10-day extinction phase aimed to reduce heroin-seeking behaviors. Following this, rats participated in a 15-minute retrieval trial with or without cues. Immediately post-retrieval, rats received bilateral injections of the actin polymerization inhibitor Latrunculin A (Lat A) into the nucleus accumbens core (NACc), a critical brain region for memory reconsolidation.</p><p><strong>Results: </strong>Immediate administration of Lat A into the NACc post-retrieval significantly reduced cue-induced and heroin-primed reinstatement of heroin-seeking behavior for at least 28 days. However, administering Lat A 6-hour post-retrieval or without a retrieval trial, as well as administering Jasplakionlide prior to memory reactivation did not affect heroin-seeking behaviors.</p><p><strong>Conclusions: </strong>Inhibiting actin polymerization during the reconsolidation window disrupts heroin-associated memory reconsolidation, leading to decreased heroin-seeking behavior and prevention of relapse. These effects are contingent upon the presence of a retrieval trial and exhibit temporal specificity, shedding light on addiction mechanisms and potential therapeutic interventions.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat. DAAO 抑制剂对精神分裂症相关认知障碍的治疗潜力:从 Luvadaxistat 中汲取经验。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae066
Ryan T Terry-Lorenzo, Reuben H Fan, Ni A Khin, Jaskaran B Singh
{"title":"Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.","authors":"Ryan T Terry-Lorenzo, Reuben H Fan, Ni A Khin, Jaskaran B Singh","doi":"10.1093/ijnp/pyae066","DOIUrl":"10.1093/ijnp/pyae066","url":null,"abstract":"<p><p>Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been proposed to underlie the pathophysiology of schizophrenia, suggesting that promoting NMDAR activity may alleviate the negative or cognitive symptoms associated with schizophrenia. To circumvent excitotoxicity that may accompany direct agonism of the glutamate binding site on the NMDAR, therapeutic trials have focused on targeting the glycine binding site on the NMDAR. Direct administration of either glycine or D-serine, both of which are endogenous coagonists at the NMDAR glycine site, has yielded mixed outcomes across an array of clinical trials investigating different doses or patient populations. Furthermore, directly administering D-serine and glycine is challenging, and thus attention has turned to alternative, indirect methods that increase endogenous D-serine and glycine levels in the brain, such as D-amino acid oxidase (DAAO) inhibitors and glycine transporter 1 inhibitors, respectively. In this review, we provide an overview of the evidence supporting the potential of NMDAR modulators in general, and DAAO inhibitors in particular, as potential adjunctive treatments for schizophrenia. We also discuss the preclinical and clinical data related to luvadaxistat, an investigational highly selective and potent DAAO inhibitor that was under development for the treatment of the cognitive impairment associated with schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxytocin Reduces Methylphenidate-Induced Dorsal Striatal Dopamine Release in Male Rhesus Macaques. 催产素减少雄性恒河猴因甲基苯甲酸引起的背纹状体多巴胺释放。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-28 DOI: 10.1093/ijnp/pyae056
Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio
{"title":"Oxytocin Reduces Methylphenidate-Induced Dorsal Striatal Dopamine Release in Male Rhesus Macaques.","authors":"Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio","doi":"10.1093/ijnp/pyae056","DOIUrl":"10.1093/ijnp/pyae056","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin is being evaluated as a potential treatment for psychostimulant use disorders. It is unknown what effect oxytocin has on dopamine signaling in response to psychostimulants in brain regions such as the striatum where oxytocin and dopamine interact to process natural rewards. We investigated the effect of oxytocin on striatal dopamine release stimulated by methylphenidate whose mechanism of action is analogous to that of cocaine.</p><p><strong>Methods: </strong>We conducted an [11C] raclopride positron emission tomography study to assess striatal dopamine release in male rhesus macaques treated with oxytocin (80 IU) (administered via the intranasal [N = 5] and intravenous [N = 6] routes) followed by methylphenidate/[11C] raclopride.</p><p><strong>Results: </strong>Oxytocin delivered by both routes significantly reduced methylphenidate-stimulated dopamine release in the dorsal striatum (caudate/putamen). These effects were, in part, evidenced by a reduction in dorsal striatal [11C] raclopride binding potential (increased dopamine release) following oxytocin administration.</p><p><strong>Conclusions: </strong>The results provide translational and mechanistic evidence for the potential role of oxytocin as a treatment for psychostimulant use disorders.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel insight into the antidepressant effect of cannabidiol: possible involvement of the 5-HT1A, CB1, GPR55, and PPARγ receptors. 大麻二酚抗抑郁作用的新见解:5-HT1A、CB1、GPR55 和 PPARγ 受体的可能参与。
IF 4.5 2区 医学
International Journal of Neuropsychopharmacology Pub Date : 2024-12-06 DOI: 10.1093/ijnp/pyae064
Yang Miao, Fei Zhao, Wei Guan
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