- |||||||||| PH10 nasal spray / VistaGen
Brain and Peripheral Tissue Distribution of Intranasal Radiolabeled Itruvone (PH10) in Laboratory Rats (Salon 4) - Apr 29, 2024 - Abstract #ASCP2024ASCP_115;
A single intranasal administration of 14C-itruvone was largely confined to the nasal passages and digestive system, with low or undetectable 14C-itruvone uptake in either peripheral (e.g., blood and blood plasma, kidney, pancreas testes/uterus) or central nervous system (CNS: olfactory lobes, cerebrum, cerebellum, and spinal cord) tissue at all time points- from 15 minutes to 168 hours after intranasal administration. Blood and plasma concentrations (ng Equivalents 14C-itruvone/g, where the lower limit of detection was <9.4 ng-eq/g), as measured by LSC, were also low, peaking at 15 minutes in males (12.3 and 21.3 ng-eq/g, respectively) and at 1 hour in female rats (88.4 and 145 ng-eq/g, respectively).
- |||||||||| Review, Journal: A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder. (Pubmed Central) - Apr 1, 2024
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.
- |||||||||| L-4-chlorokynurenine (AV-101) / VistaGen
Journal: Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101). (Pubmed Central) - Feb 6, 2024
Our pharmacogenetic analysis found that a SNP in N-acetyltransferase 8 (NAT8, rs13538) was linked to levels of N-acetyl-4-Cl-KYN relative to 4-Cl-KYN found in the plasma and that a SNP in SLC7A5 (rs28582913) was associated with the plasma levels of the active metabolite, 7-Cl-KYNA. Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters.
- |||||||||| fasedienol (PH94B NS) / VistaGen
Phase classification: PH94B in the Treatment of Adjustment Disorder With Anxiety (clinicaltrials.gov) - Dec 10, 2023
P2, N=41, Completed,
Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters. Phase classification: P2a --> P2
- |||||||||| PH10 nasal spray / VistaGen
Impaired Health-Related Quality of Life in Patients with Idiopathic Inflammatory Myopathies: A Cross-Sectional Analysis from the COVAD Dataset (Poster Hall; in person) - Sep 23, 2023 - Abstract #ACRConvergence2023ACR_Convergence_3958;
Both physical and mental health are significantly impaired in patients with IIMs particularly the elderly, IBM and those with specific comorbidities, calling for greater attention and optimized multidisciplinary care to enhance patient-reported experience and global well-being in this population. Figure 1 (A) A flow diagram of participant selection (B) Demographics and clinical characteristics of the participants included the COVAD-2 e-survey (C) Multivariable regression analysis to identify factors affecting PROMIS GMH score in patients with IIMs Figure 2: HRQoL in IIM patients, in comparison with non-IIM AIRDs, NRAIDs and Controls (A): PROMIS GPH scores (B): PROMIS GMH scores (C): PROMIS PH-10a score (D): Pain VAS score (E): PROMIS Fatigue-4a score Figure 3: HRQoL in patients with IIMs subtypes (A): PROMIS GPH scores (B): PROMIS GMH scores (C): PROMIS PH-10a score (D): Pain VAS score (E): PROMIS Fatigue-4a score
- |||||||||| Journal: Clinical specificity profile for novel rapid acting antidepressant drugs. (Pubmed Central) - Aug 9, 2023
This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs.
- |||||||||| fasedienol (PH94B NS) / VistaGen
Enrollment change, Trial termination: Palisade-2: PH94B Nasal Spray for Anxiety Induced by a Public Speaking Challenge - 2 (clinicaltrials.gov) - Jul 13, 2023
P3, N=324, Terminated,
The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs. N=208 --> 324 | Recruiting --> Terminated; Study stopped by the sponsor for business reasons and not due to any safety concerns with PH94B
- |||||||||| fasedienol (PH94B NS) / VistaGen
Trial completion, Trial primary completion date: PH94B in the Treatment of Adjustment Disorder With Anxiety (clinicaltrials.gov) - Jul 12, 2023
P2a, N=41, Completed,
N=208 --> 324 | Recruiting --> Terminated; Study stopped by the sponsor for business reasons and not due to any safety concerns with PH94B Recruiting --> Completed | Trial primary completion date: Aug 2022 --> Dec 2022
- |||||||||| Review, Journal: Novel antidepressant drugs: Beyond monoamine targets. (Pubmed Central) - Feb 27, 2023
The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.
- |||||||||| L-4-chlorokynurenine (AV-101) / VistaGen
Journal: Diversity-Oriented Biosynthesis Yields l-Kynurenine Derivative-Based Neurological Drug Candidate Collection. (Pubmed Central) - Feb 7, 2023
Our work highlights the great potential of existing enzymes in addressing long-standing synthetic challenges for facilitating the development or discovery of new drug candidates. Furthermore, our approach enables translating the reaction parameters from Eppendorf tubes to 1 L scale, affording l-4-Cl-Kyn and l-5-Cl-Kyn both on a gram scale with more than 80% isolated yields, and provides a promising alternative to further industrial applications.
- |||||||||| fasedienol (PH94B NS) / VistaGen
Trial completion date, Trial termination, Trial primary completion date: Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD) (clinicaltrials.gov) - Oct 31, 2022
P3, N=483, Terminated,
We observed no adverse effects with AV-101, which is an improvement over amantadine, with its known side effects. Trial completion date: Feb 2023 --> Sep 2022 | Recruiting --> Terminated | Trial primary completion date: Dec 2022 --> Sep 2022; Study stopped by the sponsor for business reasons and not due to any safety concerns with PH94B
- |||||||||| fasedienol (PH94B NS) / VistaGen
Trial completion: Palisade-1: PH94B Nasal Spray for Anxiety Induced by a Public Speaking Challenge (clinicaltrials.gov) - Jun 23, 2022
P3, N=209, Completed,
Trial completion date: Feb 2023 --> Sep 2022 | Recruiting --> Terminated | Trial primary completion date: Dec 2022 --> Sep 2022; Study stopped by the sponsor for business reasons and not due to any safety concerns with PH94B Active, not recruiting --> Completed
- |||||||||| aloradine nasal spray (PH94B NS) / VistaGen, Pherin Pharma
Brain and Peripheral Distribution of Intranasal Radiolabeled PH94B in Laboratory Rats (Palomino Ballroom 4-10) - May 6, 2022 - Abstract #ASCP2022ASCP_151;
One male and one female rat was used for autoradiographic analysis at each time point. A single intranasal administration of radiolabeled 14C-PH94B was largely confined to the nasal passages, with minimal or undetectable radiolabeled 14C-PH94B uptake in either peripheral (e.g. blood plasma, kidney, and liver) or central nervous system (CNS: olfactory lobes, cerebrum, cerebellum, and spinal cord) tissue at all time points- from 15 minutes to 504 hours after intranasal administration.
- |||||||||| L-4-chlorokynurenine (AV-101) / VistaGen
Journal: Does mismatch negativity have utility for NMDA receptor drug development in depression? (Pubmed Central) - Feb 19, 2022
P1, P1/2,
We conclude that the lack of standardized methodology currently prevents MMN from being ready for common use in drug discovery. This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606.
- |||||||||| L-4-chlorokynurenine (AV-101) / VistaGen
Biomarker, Enrollment change: Electrophysiological Biomarkers of AV-101 (clinicaltrials.gov) - Feb 17, 2022
P1/2, N=18, Completed,
This manuscript describes data collected from the following National Institutes of Health (NIH) and Veterans Affairs (VA) studies: AV-101, NCT03583554; lanicemine, NCT03166501; ketamine, NCT02556606. N=12 --> 18
- |||||||||| Review, Journal: Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. (Pubmed Central) - Jan 7, 2022
Furthermore, to date, most have demonstrated relatively modest effects compared with (R,S)-ketamine and esketamine, though some have shown more favorable characteristics. Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors.
- |||||||||| fasedienol (PH94B NS) / VistaGen
Enrollment open: Open-label Safety Trial of PH94B in Social Anxiety Disorder (SAD) (clinicaltrials.gov) - Dec 2, 2021
P3, N=600, Recruiting,
Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors. Not yet recruiting --> Recruiting
- |||||||||| ganaxolone oral (CCD-1042) / Marinus
Review, Journal: Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders. (Pubmed Central) - Jun 16, 2021
We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.
- |||||||||| fasedienol (PH94B NS) / VistaGen
Enrollment change, Trial completion date, Trial primary completion date: PH94B in the Treatment of Adjustment Disorder With Anxiety (clinicaltrials.gov) - May 26, 2021
P2a, N=40, Not yet recruiting,
Not yet recruiting --> Recruiting N=30 --> 40 | Trial completion date: Sep 2021 --> Nov 2022 | Trial primary completion date: Jul 2021 --> Aug 2022
- |||||||||| L-4-chlorokynurenine (AV-101) / VistaGen
Trial completion date, Trial primary completion date: AV-101 (L-4-chlorokynurenine) in Parkinson's Disease Subjects With Levodopa-Induced Dyskinesia (clinicaltrials.gov) - May 26, 2021
P2, N=20, Not yet recruiting,
N=30 --> 40 | Trial completion date: Sep 2021 --> Nov 2022 | Trial primary completion date: Jul 2021 --> Aug 2022 Trial completion date: Apr 2022 --> Apr 2024 | Trial primary completion date: Dec 2021 --> Dec 2023
- |||||||||| ketamine / Generic mfg.
Journal: Progress in the development of kynurenine and quinoline-3-carboxamide derived drugs. (Pubmed Central) - Mar 5, 2021
4-Cl-KYN has completed clinical trials in depression without success...Quinoline-3-carboxamide derivatives laquinimod, paquinimod, and tasquinimod show structural similarities to kynurenines...Further clarification may emerge from studies involving higher drug concentration, and/or from identification of ketamine targets. Clinical application trials in very diverse indications of structurally related quinoline-3-carboxamides and the wide range of their mode of action warrant further studies permitting direct comparison of effects and better target identification.
- |||||||||| Review, Journal: Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. (Pubmed Central) - Jan 12, 2021
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 and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.
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