ACS Medicinal Chemistry LettersFebruary 8, 2024Navoda Jayakodiarachchi, Mallory A Maurer, Daniel C Schultz et al.6 citations
Herein, we report the synthesis and characterization of a novel set of substituted indazole-ethanamines and indazole-tetrahydropyridines as potent serotonin receptor subtype 2 (5-HT2) agonists. Specifically, we examine the 5-HT2 pharmacology of the direct indazole analogs of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and related serotonergic tryptamines, and highlight the need for rigorous...
Psychedelic compounds, including ketamine and LSD, have gained renewed interest as potential treatments for neuropsychiatric disorders. These compounds act as psychoplastogens, promoting neuronal growth by activating AMPA receptors, TrkB, and mTOR. The prefrontal cortex plays a crucial role in their therapeutic effects through top-down control over brain regions involved in motivation, fear,...
Addressing the significant challenges of treating depression, anxiety, and substance abuse, this Patent Highlight explores the development of innovative small-molecule heterocyclic compounds as Gq-biased agonists of the 5-HT2A receptor. Unlike traditional treatments, these compounds selectively activate 5-HT2A-mediated Gq signaling, excluding related receptors like 5-HT2B and 5-HT2C. This...
Tryptamines, a class of 3-aminoethyl-indoles that activate the serotonin receptor, show potential for novel mental health treatments. The FDA has granted "breakthrough therapy designation" to psilocybin and MDMA for treatment-resistant depression, major depressive disorder, and post-traumatic stress disorder, sparking global research efforts. Various clinical trials are currently investigating...
The psychedelic N,N- dimethyltryptamine (DMT) is in clinical development for the treatment of major depressive disorder. However, when administered via intravenous infusion, its effects are short-lived due to rapid clearance. Here we describe the synthesis of deuterated analogues of DMT with the aim of prolonging the half-life and decreasing the clearance rate while maintaining similar...
Neurological diseases often involve changes in synaptic connectivity and plasticity. Psychoplastogens, substances that stimulate neuronal growth and enhance neural structures, show promise in mitigating these changes. They activate key biological targets, including AMPA receptors, TrkB, and mTOR. Substances like ketamine, scopolamine, N,N-dimethyltryptamine, and rapastinel have...
This Patent Highlight delves into the potential of next-generation therapeutics for treating mental disorders and modulating the central nervous system (CNS). Among the serotonin receptor subtypes, 5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1B have shown promise in CNS disorder treatment. Approved drugs targeting these receptors, such as antipsychotics and psychedelics, provide valuable insights into...
This viewpoint discusses integrating biomarkers, psychedelics, and AI into psychiatry for enhanced diagnostics, prognosis, and treatment. It highlights the potential of psychedelics in therapy, AI's role in predicting treatment response, and the challenges that must be addressed. The aim is to encourage research for more precise, personalized psychiatric care.
Depression is a widespread issue in the United States and the leading cause of disability globally, impacting people of all ages. Although selective serotonin reuptake inhibitors (SSRIs) are commonly used for treatment, they have limited effectiveness and may take weeks to show results. There is a pressing need for fast and effective solutions for various types of depression, including chronic,...
This Patent Highlight presents a method to treat inflammatory or neurological disorders in subjects needing treatment. The method involves administering a therapeutically effective amount of a composition containing a subhallucinogenic concentration of substituted phenethylamine. The substituted phenethylamine may belong to the 2C-X family, including 2C-H, 2C-I, 2C-B, or 2C-E. The specific...
This Viewpoint discusses the intersection of targeted protein degradation (TPD) technologies and psychedelic research. The resurgence in interest in psychedelics for treating mental disorders and the known genetic variability in responses require new strategies. TPD technologies might address this variability, modulating protein expressions based on genetic profiles. The discussion includes...
The gut-brain axis (GBA) refers to the sophisticated bidirectional communication system connecting the digestive system with the central nervous system. This interaction is enabled by a series of intricate signaling processes, encompassing various neuro-immune and hormonal pathways. The association between the gut microbiome and mental health has garnered immense scientific and public interest,...
This Patent Highlight describes derivatives of DMT, 5-MeO-DMT, and MDMA that are metabolically converted to biologically active analogs. When these prodrugs are administered to a subject, they potentially could be used therapeutically in conditions associated with neurological diseases. Furthermore, the disclosure provides methods to potentially treat conditions comprising major depressive...
The renaissance of research into psychedelics class of drugs has renewed interest for a possible psychedelic clinical therapy for treating psychiatric conditions such as treatment-resistant depression, major depressive-disorder, post-traumatic stress disorder, and other neuropsychiatric diseases. Psychedelics are known to stimulate neurogenesis and gliogenesis, reduce inflammation, and...
Provided herein are MDMA and their analogs for the potential psychotherapy-assisted treatment of alcohol use disorder (AUD), post-traumatic stress disorder (PTSD), and a method of predicting dosing and patient response.
ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTApplication of Deuterated N,N-Dimethyltryptamine in the Potential Treatment of Psychiatric and Neurological DisordersRobert B. Kargbo*Robert B. KargboUsona Institute, Fitchburg, Wisconsin 53711-5300, United States*E-mail: [email protected]More by Robert B. Kargbohttps://orcid.org/0000-0002-5539-6343Cite this: ACS Med. Chem. Lett. 2022, 13, 9,...
ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTIbogaine and Their Analogs as Therapeutics for Neurological and Psychiatric DisordersRobert B. Kargbo*Robert B. KargboUsona Institute, 277 Granada Drive, San Luis Obispo, California 93401-7337, United States*[email protected]More by Robert B. Kargbohttps://orcid.org/0000-0002-5539-6343Cite this: ACS Med. Chem. Lett. 2022, 13, 6,...
ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTThe Psychedelic Renaissance: Addressing Potential Adverse Effects in a Therapeutic SettingRobert B. Kargbo*Robert B. KargboUsona Institute, 277 Granada Drive, San Luis Obispo, California 93401-7337, United States*Email: [email protected]More by Robert B. Kargbohttps://orcid.org/0000-0002-5539-6343Cite this: ACS Med. Chem. Lett. 2021, 12, 12,...
ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXT5-MeO-DMT: Potential Use of Psychedelic-Induced Experiences in the Treatment of Psychological DisordersRobert B. Kargbo*Robert B. KargboUsona Institute, 277 Granada Drive, San Luis Obispo, California 93401-7337, United States*Email: [email protected]More by Robert B. Kargbohttps://orcid.org/0000-0002-5539-6343Cite this: ACS Med. Chem. Lett....
Psilocybin, an active component in "magic mushroom", may have the potential to meet the therapeutic needs for a number of indications without the addictiveness and overdose risk of other mind-altering drugs, such as cocaine, heroin, alcohol, methamphetamine, and so forth. The need for new therapies is urgent because addiction, overdose, and suicide deaths have risen throughout the United States...