Article
Biochemistry & Molecular Biology
Giorgia Boero, Minna H. Mcfarland, Ryan E. Tyler, Todd K. O'Buckley, Samantha L. Chery, Donita L. Robinson, Joyce Besheer, A. Leslie Morrow
Summary: The neurosteroid 3 alpha,5 alpha-THP regulates the stress response of HPA axis and its effects depend on sex, brain region, and stressor. This study investigates the behavioral effects of 3 alpha,5 alpha-THP during forced swim stress and its interaction with the opioid system. The findings suggest that this interaction may have implications for the treatment of neuropsychiatric disorders involving HPA axis activation.
Review
Neurosciences
Sara Carlini, Lauren M. Osborne, Kristina M. Deligiannidis
Summary: Postpartum depression has negative effects on childbearing persons globally. Current treatments have limited evidence, while hormonal treatments have rationality but limited efficacy. In contrast, the development of antidepressants with allopregnanolone analogues has shown promise.
DIALOGUES IN CLINICAL NEUROSCIENCE
(2023)
Review
Endocrinology & Metabolism
Peter M. Lambert, Xinguo Lu, Charles F. Zorumski, Steven Mennerick
Summary: The rise of ketamine and brexanolone as rapid antidepressant treatments has prompted research into their common mechanisms. These drugs have distinct characteristics compared to traditional antidepressants in terms of onset time and duration of effect. Based on existing studies, network disinhibition and increased high-frequency oscillations are potential mechanisms underlying the acute effects of rapid antidepressants.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Review
Psychiatry
Amber N. Edinoff, Amira S. Odisho, Kendall Lewis, Amir Kaskas, Grace Hunt, Elyse M. Cornett, Alan D. Kaye, Adam Kaye, John Morgan, P. Scott Barrilleaux, David Lewis, Omar Viswanath, Ivan Urits
Summary: Postpartum depression is a significant type of postpartum psychiatric syndrome that affects the mother-child bond. Allopregnanolone and its analog brexanolone play important roles in modulating GABA receptors, leading to improvements in depression scores.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Giorgia Boero, Ryan E. Tyler, Todd K. O'Buckley, Irina Balan, Joyce Besheer, A. Leslie Morrow
Summary: This study found that 3 alpha,5 alpha-THP has different regulatory effects on stress response in male and female rats. 3 alpha,5 alpha-THP can reduce the increase of circulating corticosterone after stress and have different effects on the expression levels of hypothalamic CRF, CRFR1, CRFBP, POMC, and GR. These results suggest that gender differences and stress types play important roles in the regulation of the HPA axis by 3 alpha,5 alpha-THP.
Review
Neurosciences
Doodipala Samba Reddy, Robert H. H. Mbilinyi, Emily Estes
Summary: This article discusses the critical role of neurosteroids in postpartum depression (PPD) and introduces the breakthrough antidepressant brexanolone as a first-in-class neurosteroid therapy. PPD, a neuroendocrine disorder affecting 20% of mothers, is characterized by symptoms such as persistent sadness, fatigue, dysphoria, and disruptions in cognition, emotion, appetite, and sleep. The main pathology behind PPD is the reduction of neurosteroids after childbirth, known as neurosteroid withdrawal. Brexanolone, a progesterone-derived allopregnanolone, rapidly alleviates anxiety and mood deficits by activating GABA-A receptors, making it a transformative treatment for PPD with significant advantages over traditional antidepressants.
PSYCHOPHARMACOLOGY
(2023)
Article
Substance Abuse
Laura C. Ornelas, Giorgia Boero, Kalynn Van Voorhies, Todd K. O'Buckley, Joyce Besheer, A. Leslie Morrow
Summary: Alcohol affects multiple circuits in the brain, disrupting the balance between inhibitory GABA transmission and excitatory glutamate signaling. The loss of GABAergic inhibition is associated with the development of alcohol addiction. The neurosteroid 3 alpha,5 alpha-THP can regulate alcohol self-administration in female rats by increasing its expression in the AcbC.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Alba Garcia-Baos, Ines Gallego-Landin, Irene Ferreres-Alvarez, Xavier Puig-Reyne, Adriana Castro-Zavala, Olga Valverde, Ana Martin-Sanchez
Summary: This study compares the effectiveness of allopregnanolone and ketamine in a mouse model of postpartum depression (PPD). The results suggest that ketamine may be more effective than allopregnanolone in treating PPD. Additionally, the mouse model used in this study recapitulates the core symptoms and molecular alterations seen in PPD patients.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Jennifer L. Payne
Summary: Brexanolone is a novel treatment option for postpartum depression, acting as a positive allosteric modulator of the GABAA receptor. It has shown rapid onset of action and sustained effects without continued administration, making it suitable for women with moderate to severe PPD. Further research is needed to confirm the efficacy of the current recommended dosing regimen.
EXPERT OPINION ON PHARMACOTHERAPY
(2021)
Article
Behavioral Sciences
Gabriele Floris, Gino Paolo Asuni, Giuseppe Talani, Francesca Biggio, Maria Giuseppina Pisu, Mary Tresa Zanda, Liliana Contu, Elisabetta Maciocco, Mariangela Serra, Paolo Follesa
Summary: This study investigates the role of the GABA(B)R receptor in alcohol consumption and preference in mice. The results show that mice lacking functional GABA(B)R drink more alcohol, prefer alcohol over water, and have higher blood alcohol concentrations compared to wild-type mice. Additionally, the study suggests that the GABA(B)R receptor modulates the activity of GABA(A) receptors in the hippocampus, potentially influencing alcohol preference in mice.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Carmen J. Zamora-Sanchez, Ignacio Camacho-Arroyo
Summary: Allopregnanolone is a extensively studied progesterone metabolite and its synthetic analogs are evaluated as therapeutic agents for anxiety and depression. Recent research has shown that 3 alpha-THP has dual-regulatory effects on the development of certain cancers. This review explores the metabolism and mechanisms of action of 3 alpha-THP in both normal and tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Elisavet Kaltsouni, Patrick M. Fisher, Manon Dubol, Steinar Hustad, Rupert Lanzenberger, Vibe G. Frokjaer, Johan Wikstrom, Erika Comasco, Inger Sundstrom-Poromaa
Summary: PMDD is a psychiatric condition that affects about 5% of women in their reproductive age, characterized by emotional and physical impairments. This study showed that treating PMDD patients with SPRM resulted in enhanced brain reactivity during aggressive responses, particularly in the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Cheng Huang, Yun Wu, Na Zhai, Xiulian Ju, Chunqing Zhao, Xiaogang Luo, Yoshihisa Ozoe, Genyan Liu
Summary: In this study, a series of novel compounds 4-APIs were found to have insecticidal activity, with the most potent antagonist being the 4-(1,1'-biphenylyl) analog. The docking studies suggested that the Jr-Jr stacking interactions may contribute to the antagonism by this compound. These findings provide important information for designing novel iGABAR antagonists and suggest that the 4-APIs could be potential leads for further insecticide development.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Review
Endocrinology & Metabolism
Graziano Pinna
Summary: Mood disorders are common psychiatric conditions that have a significant economic burden and are poorly diagnosed and treated. The lack of biomarkers for personalized treatment is a major challenge. Recent studies have identified potential pharmacological targets, such as neurosteroid biosynthesis and the endocannabinoid system, but more research is needed to assess their efficacy in diagnosis and treatment.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Chemistry, Organic
Qiwen Gao, Jinhong Tian, Kangmei Wen, Chen Chen, Xingang Yao, Jianxin Pang, Xiaodong Tang
Summary: In this study, a copper-mediated C4-benzylation reaction of 5-aminopyrazoles with 3-indoleacetic acids was presented. Various benzylated 5-aminopyrazoles were synthesized in good-to-excellent yields under basic and ligand-free conditions in the presence of copper acetate. The benzylation method was also applied to other substrates and showed potential antiproliferative activities against cancer cell lines. Moreover, the C4-benzylated products underwent cyclization with aldehydes to form 1H-pyrazolo-[4 ',3 ':6,7]-azepino-[3,4-b]-indoles via one-pot two-step processes. The cyclized products exhibited fluorescence emissions with large Stokes shifts.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
