JNJ-18038683 / J&J - LARVOL DELTA

Improving Cognition in Bipolar Disorder: A Systematic Review of Current Pharmacological and Nutraceutical Approaches. (PubMed, Neuropsychobiology) - "These results suggest possible approaches for improving cognitive functioning in individuals with BD. Nevertheless, the inconsistency in outcomes and differences in study methodologies highlight the need for larger, rigorously controlled trials with uniform cognitive evaluations to confirm these findings and to assess their clinical relevance."

Journal • Review • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry

5-HT7 antagonists confer analgesia via suppression of neurotrophin overproduction in submucosal nerves of mouse models with visceral hypersensitivity. (PubMed, J Physiol) - "Selective 5-HT7 antagonists [CYY1005 (CYY), JNJ-18038683 (JNJ) or SB269970 (SB7)] were orogavaged to an IBS-like mouse model of postinflammatory VH after resolution from trinitrobenzene sulfonic acid-induced colitis...Activation of 5-HT7 promotes neurite elongation in primary submucosal nerve cultures. The findings implicate a potential role of submucosal plexus in 5-HT7-dependent visceral hypersensitivity."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Pain • CDC42

Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder. (PubMed, J Clin Psychopharmacol) - "This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo."

Clinical • Journal • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Psychiatry • Sleep Disorder

Selective 5-hydroxytryptamine receptor 7 antagonism influences neural activation during visuospatial memory task (ECNP 2023) - "Two medications with 5HT 7 antagonist properties, Vortioxetine and Lurasidone, have been shown to improve symptoms of cognitive impairment in major depressive disorder and schizophrenia respectively [1-2]. Conclusions We found that administration of JNJ-18038683, a selective high affinity functional 5HT 7 receptor antagonist, was associated with significantly increased task-related brain activations in the dorsolateral prefrontal cortex during a visuospatial memory task in healthy participants. While there were no differences in task performance, increased brain activations associated with JNJ-18038683 administration could be related to greater engagement of brain regions integral to attention and working memory."

Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia

Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Herbert Meltzer | Active, not recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • CORIN

Design and discovery of a high affinity, selective and β-arrestin biased 5-HT Receptor Agonist. (PubMed, Med Chem Res) - "Although 2a showed about 8 times less activity than 5-HT in the Gs pathway, it showed over 31 times higher activity than 5-HT in the β-arrestin pathway. This constitutes a significant β-arrestin pathway preference and shows 2a to be more potent and more efficacious than the recently published β-arrestin biased 3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine, the N-debenzylated analog of JNJ18038683 (Compound 7)."

Journal

Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients (clinicaltrials.gov) - P2; N=60; Active, not recruiting; Sponsor: Herbert Meltzer; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2021 ➔ Dec 2022

Clinical • Enrollment closed • Trial completion date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Herbert Meltzer; Trial completion date: Oct 2019 ➔ Dec 2021; Trial primary completion date: Jul 2019 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Imaging 5HT7 Antagonist Effects in Bipolar Disorder (clinicaltrials.gov) - P=N/A; N=68; Recruiting; Sponsor: King's College London; Trial completion date: Jul 2020 ➔ Jun 2022; Trial primary completion date: May 2020 ➔ Jun 2022

Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry

[VIRTUAL] 5-HT7 Receptor and Mood Disorders—Depression, Bipolar and Anxiety: A Systematic Review (CINP 2021) - "Depression: SB-269970, N-biphenyl-2-ylmethyl2-methoxyphen ylpiperazinylalkanamides, Lu AA21004, HBK-15, a PZ-1417 and PZ-1150 are used as 5HT-7 receptor antagonists, and reduced mice immobility in animal tests suggesting that they may have antidepressant properties (Hedlund et al., 2005; Wesolowska et al, 2006a, 2006b; Bonaventure et al., 2007; Sarkisyan et al., 2010; Medina et al., 2014; Zhang et al., 2015; Canale et al., 2016; Canale et al., 2014; Guilloux et al., 2013; Pytka et al., 2015)...Bipolar disorder: Researchers at Northwest University (U.S.A.) are testing whether JNJ-18038683 can improve cognition and reduce depressive symptoms in bipolar patients... The 5-HT7 receptor has strong connections with anxiety and depression. Being dosed with 5-HT7 antagonists, rodents demonstrated anxiolytic behaviours in experiments. Regarding depression, when being dosed with 5-HT7 antagonists, animals’ reduction of immobility was detected."

Review • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Preliminary evaluation of novel serotonin antagonists as potential antidepressant agents (ACS-Fall 2018) - "...Specifically, the selective 5-HT7 antagonists SB-269970 and JNJ-18038683 have been shown to induce antidepressant-like activity...In addition, SB-269970 demonstrated a significantly faster antidepressant response in olfactory bulbectomized rats when compared to fluoxetine...The binding data, physicochemical properties, and in vitro ADME data for this series of novel 5-HT7 selective ligands will be discussed. The pharmacokinetic data for compound(s) selected to undergo animal models of depression will also be presented."

Biosimilar • CNS Disorders • Depression • Mood Disorders