zanvipixant (JNJ-55308942) / J&J - LARVOL DELTA

Fire and Ice: From Early Trauma Through P2X7 Receptor-Mediated Neuroinflammation to Depression and Anxiety – a review (ECNP 2025) - "Novel brain-penetrant P2X7R antagonists, such as JNJ-54175446 and JNJ-55308942, are currently undergoing phase 2 clinical trials for depression, reflecting growing interest in the receptor's translational potential. This review highlights the intersection of P2X7R signalling, ELS, and psychiatric disorders, emphasizing both indirect pathways through chronic neuroinflammation and direct genetic associations via P2RX7 variants. By integrating findings across species and methodologies, the review underscores the significance of this receptor as a molecular mediator of stress vulnerability. Elucidating the interplay between P2X7R and early adversity is crucial, as it could pave the way for personalized interventions tailored to individuals with a history of trauma.Dora Torok is supported by EKÖP-2024-68."

Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • IL1B • IL6 • TNFA

Triazole-Based Radioligands for PET of P2X7R: Syntheses, Conformational Studies, and Preliminary Autoradiographic Evaluation of [18F]AM-10. (PubMed, ACS Omega) - "In this work, we focus on five triazole-based ligands with high affinity and selectivity for P2X7 receptors (JNJ-64413739, JNJ-55308942, AM-10, AM-12, and AM-15), which are amenable to autoradiography and positron emission tomography (PET) imaging...Quantitative autoradiography with [ 18 F]-AM-10 in sagittal mouse brain cryostat sections indicated a maximum specific binding (B max) of 15.8 ± 2.8 pmol/g of wet weight and a dissociation constant (K D) of 16.6 ± 5.1 nM. Thus, we present the first synthesis of [ 18 F]-AM-10 by isotopic exchange and confirm its specific binding at mouse brain P2X7 receptors, which should warrant its use in animal and human PET investigations."

Journal • Inflammation

Continuous-flow synthesis of 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridines towards key intermediates of clinical candidates JNJ-54175446 and zanvipixant (JNJ-55308942) with antidepressant activity. (PubMed, RSC Adv) - "Applying the optimized conditions, yields of 48% (58% regioselectivity) and 45% (91% regioselectivity) were achieved, respectively. The method ensures safe utilization of azide in the cycloaddition, and uses a safer oxidant for the elimination, offering a scalable and affordable alternative synthetic route."

Journal • CNS Disorders • Depression • Inflammation • Psychiatry

Complement Molecule C3a Exacerbates Early Brain Injury After Subarachnoid Hemorrhage by Inducing Neuroinflammation Through the C3aR-ERK-P2X7-NLRP3 Inflammasome Signaling Axis. (PubMed, Inflammation) - "Further addition of JNJ-55308942 (a P2X7R antagonist) revealed that C3a activated the NLRP3 inflammasome via P2X7...Overall, C3a exacerbates EBI-associated NLRP3 inflammasome and neuroinflammation via the C3aR-ERK-P2X7 pathway after SAH. Inhibiting C3aR may serve as a one possible treatment approach to alleviate SAH after EBI."

Journal • CNS Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • Vascular Neurology • IL10 • IL1B • IL6 • ITGAM • NLRP3 • TNFA

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=116 | Completed | Sponsor: Janssen Pharmaceutica N.V., Belgium | Active, not recruiting ➔ Completed

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

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=116 | Active, not recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Recruiting ➔ Active, not recruiting

Enrollment closed • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=115 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Trial completion date: Mar 2025 ➔ May 2024

Trial completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=164 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Trial completion date: May 2024 ➔ Mar 2025

Trial completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=164 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Not yet recruiting ➔ Recruiting

Enrollment open • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

A Clinical Study to Investigate the Efficacy, Safety and Tolerability of JNJ-55308942 in Bipolar Depression (clinicaltrialsregister.eu) - P2 | N=164 | Ongoing | Sponsor: Janssen-Cilag International NV

New P2 trial • Bipolar Disorder • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

A Study of JNJ-55308942 in the Treatment of Bipolar Depression (clinicaltrials.gov) - P2 | N=164 | Not yet recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium

New P2 trial • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry