verucerfont (GSK-561679) / Neurocrine, GSK - LARVOL DELTA

Stress-free blood sampling in minipigs: A novel method for assessing 24-h cortisol profiles and drug effects on diurnal and ultradian rhythms. (PubMed, J Pharmacol Toxicol Methods) - "To validate our model, we investigated the effects of Verucerfont, a CRH receptor antagonist, and Venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Venlafaxine maintained plasma concentrations within the targeted human effective range. This method enables us to enhance our understanding of cortisol regulation and provide valuable insights for the impact of investigation drugs on the diurnal and ultradian rhythms of cortisol."

Journal

A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder. (PubMed, Drugs) - "Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders."

Journal • Review • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

CPG and Non-CPG Epigenomic Mapping in Human Cortical Neurons Reveals Hydroxymethylation as an Important Gene Regulatory Mechanism in PTSD (WCPG 2022) - "Drug repurposing analysis suggests that the PTSD-associated genes identified here, with a predicted transcription factor binding site in the modified cytosine, could encode possible targets for drug action: PRAMIPEXOLE as an agonist of DRD4, VERUCERFONT, ONO-2333MS, PEXACERFONT, SSR125543 and ANTALARMIN as inhibitors of CRHR1. Including more than 1.5M cytosines in the analyses, a total of 745 cytosines were differentially methylated, 539 at CpG and 206 at non-CpG sites. For 5hmC, 975 differential cytosines were identified, 816 at CpG and 159 at non-CpG sites. Developmental processes, immune systems response, and response to stimulus (such as response to growth factor stimulus, wounding, estrogen) were enriched by both mechanisms, although higher significances were observed in 5hmC."

CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • ACKR3 • ER • FLT4 • HSP90AA1 • LTBP2 • NGFR

Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients. (PubMed, Psychophysiology) - "While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD."

Biomarker • Clinical • Journal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Corticotropin-Releasing Factor Receptor 1 Antagonism Is Ineffective for Women With Posttraumatic Stress Disorder. (PubMed, Biol Psychiatry) - "The results of this trial, the first evaluating a CRF1 receptor antagonist for the treatment of PTSD, combined with other negative trials of CRF1 receptor antagonists for major depressive disorder, generalized anxiety disorder, and social anxiety disorder, suggest that CRF1 receptor antagonists lack efficacy as monotherapy agents for these conditions."

Journal • Biosimilar • CNS Disorders • Depression • Post-traumatic Stress Disorder

Safety, Pharmacokinetics and Pharmacodynamics of NBI-77860 in Adolescent Females With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P1; N=15; Recruiting; Sponsor: Neurocrine Biosciences; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar

Analyzing Female Trauma Exposed Responses to a Medication (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: Department of Veterans Affairs; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar

DNA methylation levels are associated with CRF receptor antagonist treatment outcome in women with post-traumatic stress disorder. (PubMed, Clin Epigenetics) - P2; "Our results support a possible role of CRHR1 methylation levels as an epigenetic marker to track response to CRF antagonist treatment in biologically relevant subgroups. Moreover, pre-treatment NR3C1 methylation levels may serve as a potential marker to predict PTSD treatment outcome, independent of the type of therapy. However, to establish clinical relevance of these markers, our findings require replication and validation in larger studies."

Clinical • Journal