JNJ-18038683 / J&J - LARVOL DELTA

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