D-cycloserine (JNX4022) / Junaxo - LARVOL DELTA

Pharmacological-assisted Psychotherapy for Post-Traumatic Stress Disorder: a systematic review and meta-analysis. (PubMed, Eur J Psychotraumatol) - " MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions."

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

Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis. (PubMed, Int J Infect Dis) - "We observed a high incidence of early neuropsychiatric toxicity in this cohort of patients treated with terizidone. Cycloserine clearance and higher doses of pyridoxine are associated with incident or worsening peripheral neuropathy."

Journal • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Pain • Psychiatry • Respiratory Diseases • Tuberculosis

[VIRTUAL] Maintenance of Antidepressant and Antisuicidal Effects of D-cycloserine among Patients with Treatment-Resistant Depression Who Responded to Low-Dose Ketamine Infusion: A Randomized, Double-Blind Study (CINP 2021) - "Despite the maintenance of antidepressant effect of ketamine infusion did not differ between DCS and placebo groups, our findings supported a superior maintenance of antisuicidal effect in DCS than in placebo. DCS may be therapeutically beneficial for patients with TRD who responded to ketamine infusion but still had the suicidal risk."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Imaginal Exposure & D-Cycloserine (DCS) for Posttraumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P=N/A; N=72; Terminated; Sponsor: Weill Medical College of Cornell University; N=124 ➔ 72; Recruiting ➔ Terminated; Trial is no longer enrolling due to priority of other non-pharmacologic PTSD trials.

Enrollment change • Trial termination • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

PIPLE: Pain, Learning, and Nocebo (clinicaltrials.gov) - P=N/A; N=50; Not yet recruiting; Sponsor: Leiden University Medical Center

New trial • Musculoskeletal Pain • Pain

The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder. (PubMed, Cochrane Database Syst Rev) - "The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings."

Adverse events • Clinical • Journal • Review • Autism Spectrum Disorder • Genetic Disorders

Human perceptual learning is delayed by the N-methyl-D-aspartate receptor partial agonist D-cycloserine. (PubMed, J Psychopharmacol) - "In sum, we provide first evidence for modulation of perceptual learning by administration of a partial N-methyl-D-aspartate agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains."

Journal

Multimodal Cue Exposure Therapy for Smoking Cessation (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Boston University Charles River Campus; N=240 ➔ 0; Trial completion date: Aug 2024 ➔ Jan 2021; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Aug 2024 ➔ Jan 2021

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Tobacco Cessation

Vancomycin's potency against Mycobacterium tuberculosis in the hollow fiber system model. (PubMed, J Glob Antimicrob Resist) - "Our proof-of-concept studies show that vancomycin optimal exposure target for Mtb kill could be achieved via the inhalational route drug delivery. Addition of drugs such as D-cycloserine that are synergistic with vancomycin may lower the vancomycin concentrations required to kill Mtb."

Journal • Infectious Disease • Respiratory Diseases • Tuberculosis

Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019-2020. (PubMed, Monaldi Arch Chest Dis) - "Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine...Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted."

Clinical • Journal • Diabetes • Gastroenterology • Gastrointestinal Disorder • Hepatitis C Virus • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Pain • Psychiatry • Respiratory Diseases • Tuberculosis

TB-TRUSTplus: Refining MDR-TB Treatment (T) Regimens (R) for Ultra(U) Short(S) Therapy(T)-PLUS (clinicaltrials.gov) - P=N/A; N=200; Recruiting; Sponsor: Huashan Hospital

New trial • Infectious Disease • Respiratory Diseases • Tuberculosis

Stress-induced resistance to fear memory destabilization is associated with an impairment of Lys-48-linked protein polyubiquitination in the Basolateral Amygdala: influence of D-cycloserine. (PubMed, Neurobiol Learn Mem) - "In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to furthercharacterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling,protein degradation and memory destabilization in stress-induced resistant memories."

Journal • Targeted Protein Degradation

Cycloserine rTMS Plasticity Augmentation in Depression (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: University of Calgary; Recruiting ➔ Active, not recruiting; Trial completion date: Jan 2021 ➔ Sep 2021; Trial primary completion date: Sep 2020 ➔ Dec 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Immunology • Mood Disorders • Psychiatry

Adjunctive D-Cycloserine in Major Depressive Disorder (clinicaltrials.gov) - P2; N=50; Active, not recruiting; Sponsor: University of Calgary; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Depression • Immunology • Mood Disorders • Psychiatry • MRI

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. (PubMed, Front Psychiatry) - "This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current..."

Journal • Review • CNS Disorders • Depression • General Anxiety Disorder • Mental Retardation • Mood Disorders • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Social Anxiety Disorder

Efficacy of adjunctive D-Cycloserine for the treatment of schizophrenia: a systematic review and meta-analysis of randomized controlled trials. (PubMed, J Neural Transm (Vienna)) - "I values for heterogeneity were 61%, 67%, and 0% for studies assessing negative, cognitive, and positive symptom ratings, respectively. D-Cycloserine did not exhibit significant efficacy in treating negative, cognitive, or positive symptoms of schizophrenia at either study-defined endpoint (4-36 weeks) or at four weeks (early outcome)."

Journal • Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

Facilitation of GluN2C-containing NMDA receptors in the external globus pallidus increases firing of fast spiking neurons and improves motor function in a hemiparkinsonian mouse model. (PubMed, Neurobiol Dis) - "In contrast, facilitating the function of GluN2C-containing receptors using glycine-site NMDA receptor agonists, D-cycloserine (DCS) or AICP, increased the spontaneous firing frequency of PV neurons in a GluN2C-dependent manner. Finally, we demonstrate that local infusion of DCS or AICP into the GPe improved motor function in a mouse model of PD. Together, these results demonstrate that GluN2C-containing receptors and potentially GluN2D-containing receptors in the GPe may serve as a therapeutic target for alleviating motor dysfunction in PD and related disorders."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study of the Participation of NMDA Glutamate Receptors in the Mechanisms of Specific Anterograde Amnesia Reversion. (PubMed, Bull Exp Biol Med) - "It was shown that D-cycloserine in amnestic snails did not affect the food reactions caused by the presentation of a conditioned stimulus during the reminder (without combination with the unconditioned stimulus). It is assumed that NMDA glutamate receptors in amnestic animals are involved in the neural plasticity mechanisms that underlie short-term memory, but their activation does not influence the anterograde amnesia processes and does not lead to the formation or recovery of long-term memory."

Journal • CNS Disorders

[VIRTUAL] Myoclonus-associated GRIN1 variant: from molecular mechanism to rescue pharmacology (AES 2020) - "Three NMDAR positive allosteric modulators (24(S)-hydroxycholesterol, pregnenolone sulfate, and tobramycin) and three co-agonists at glycine site (L-serine, D-serine, and D-cycloserine) showed a similar potentiation effects or a similar potency for WT and variant GluN1-P532H-containing NMDARs... Taken together, these data suggest the variant receptor is a loss-of-function variant with decreased agonist potency, shortened synaptic response time course, and reduced channel open probability. Evaluation of positive allosteric modulators may explore the possibility to use these compounds to partially rectify some functional deficits of the loss-of-function variant. Funding: During this work, HY was supported by NIH - the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [grant R01HD082373], by the University Research Committee (URC; #00085889) from Emory University, and by a research grant from Sage Therapeutics to Emory University..."

Cardiovascular • CNS Disorders • Developmental Disorders • Mental Retardation • Movement Disorders

Integron gene cassettes harboring novel variants of D-alanine-D-alanine ligase confer high-level resistance to D-cycloserine. (PubMed, Sci Rep) - "Molecular dynamics simulations were used to explain the mechanism of this phenotypic change at the atomic scale. A hypothesis for the evolutionary selection of ddl containing integron gene cassettes is proposed, based on molecular docking of plant metabolites within the ATP and D-cycloserine binding pockets of Ddl."

Journal

Inhibition of Campylobacter jejuni Biofilm Formation by D-Amino Acids. (PubMed, Antibiotics (Basel)) - "In addition, a mixture of DAs enhanced antimicrobial efficacy of D-Cycloserine (DCS) up to 32% as compared with DCS treatment alone...Furthermore, L-alanine and D-tryptophan decreased transcript levels of peptidoglycan biosynthesis enzymes alanine racemase (alr) and D-alanine-D-alanine ligase (ddlA) while D-serine was only able to decrease the transcript levels of alr. Our findings suggest that a combination of DAs could reduce biofilm formation, viability and persistence of C. jejuni through dysregulation of alr and ddlA."

Journal

Survey of NMDA receptor-related biomarkers for depression. (PubMed, Curr Pharm Des) - "Furthermore, NMDAR ligands, such as ketamine and Dcycloserine, have shown antidepressive effects in several studies. Various related enzymes and transporters that play a role in the modulation of NMDAR neurotransmission were also surveyed. This review aims to investigate NMDAR related metabolism, which may serve as feasible indicators for MDD and may contribute to further exploration of reliable biomarkers for MDD and promote new treatment of depression."

Biomarker • Journal • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Psychiatry

AIH for Spinal Cord Repair (clinicaltrials.gov) - P1; N=175; Recruiting; Sponsor: VA Office of Research and Development; Not yet recruiting ➔ Recruiting

Enrollment open

Prevalence of Antibiotic-Resistant Pulmonary Tuberculosis in Bangladesh: A Systematic Review and Meta-Analysis. (PubMed, Antibiotics (Basel)) - "Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended."

Journal • Retrospective data • Review • Infectious Disease • Tuberculosis

Enhanced exposure therapy for combat-related Posttraumatic Stress Disorder (PTSD): Study protocol for a randomized controlled trial. (PubMed, Contemp Clin Trials) - P3 | "This study is the first to compare the relative efficacy of DCS-augmented VRE versus PE on PTSD symptoms. The design has several advantages: participants received an active, effective treatment and predictors of response to treatment included genetic and psychobiological measures. The results may directly influence the future delivery of services, and contribute to the development of a standardized treatment protocol."

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