Abstract
Tetrahydroprotoberberines (THPBs) represent a series of compounds extracted from the Chinese herb Corydalis ambigua and various species of Stephania. THPBs, dependent on the presence of hydroxyl groups in its structure, are divided into three types: nonhydroxyl- THPBs, monohydroxyl-THPBs and dihydroxyl-THPBs. THPBs are identified as a new category of dopamine receptor ligands. Among all THPBs, dihydroxyl-THPBs attracted particular attention because of their dual actions on dopamine (DA) receptors. They exhibit D1 receptor agonistic activity while acting as D2 receptor antagonists. This unique pharmacological profile made dihydroxyl-THPBs such as l-stepholidine (l-SPD) potential agents in the treatment of drug addiction, Parkinsons disease, and especially, schizophrenia. Clinical studies have shown that co-administration of l-SPD with a typical antipsychotic drug significantly enhances the therapeutic effects and remarkably reduces the tardive dyskinesia induced by the typical antipsychotic drug used with schizophrenic patients. Moreover, l-SPD alone was shown to have therapeutic value without inducing significant extrapyramidal side effects and also seemed to reduce the negative symptoms of schizophrenia. This is confirmed in experimental studies using animal models of schizophrenia, in which l- SPD improved social interaction and cognitive function, inhibited hyperactivity in schizophrenic animals. This review discusses the chemistry, pharmacology and clinical implications of l-THPBs in the drug development for psychosis and neurobiological diseases.
Keywords: Tetrahydroprotoberberines, l-stepholidine, dopamine, receptor, schizophrenia, agonist, antagonist
Current Medicinal Chemistry
Title: Recent Developments in Studies of l-Stepholidine and its Analogs: Chemistry, Pharmacology and Clinical Implications
Volume: 14 Issue: 28
Author(s): Jiao Mo, Yang Guo, Yu-She Yang, Jing-Shan Shen, Guo-Zhang Jin and Xuechu Zhen
Affiliation:
Keywords: Tetrahydroprotoberberines, l-stepholidine, dopamine, receptor, schizophrenia, agonist, antagonist
Abstract: Tetrahydroprotoberberines (THPBs) represent a series of compounds extracted from the Chinese herb Corydalis ambigua and various species of Stephania. THPBs, dependent on the presence of hydroxyl groups in its structure, are divided into three types: nonhydroxyl- THPBs, monohydroxyl-THPBs and dihydroxyl-THPBs. THPBs are identified as a new category of dopamine receptor ligands. Among all THPBs, dihydroxyl-THPBs attracted particular attention because of their dual actions on dopamine (DA) receptors. They exhibit D1 receptor agonistic activity while acting as D2 receptor antagonists. This unique pharmacological profile made dihydroxyl-THPBs such as l-stepholidine (l-SPD) potential agents in the treatment of drug addiction, Parkinsons disease, and especially, schizophrenia. Clinical studies have shown that co-administration of l-SPD with a typical antipsychotic drug significantly enhances the therapeutic effects and remarkably reduces the tardive dyskinesia induced by the typical antipsychotic drug used with schizophrenic patients. Moreover, l-SPD alone was shown to have therapeutic value without inducing significant extrapyramidal side effects and also seemed to reduce the negative symptoms of schizophrenia. This is confirmed in experimental studies using animal models of schizophrenia, in which l- SPD improved social interaction and cognitive function, inhibited hyperactivity in schizophrenic animals. This review discusses the chemistry, pharmacology and clinical implications of l-THPBs in the drug development for psychosis and neurobiological diseases.
Export Options
About this article
Cite this article as:
Mo Jiao, Guo Yang, Yang Yu-She, Shen Jing-Shan, Jin Guo-Zhang and Zhen Xuechu, Recent Developments in Studies of l-Stepholidine and its Analogs: Chemistry, Pharmacology and Clinical Implications, Current Medicinal Chemistry 2007; 14 (28) . https://dx.doi.org/10.2174/092986707782794050
DOI https://dx.doi.org/10.2174/092986707782794050 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Dopamine Receptor Interacting Proteins: Targeting Neuronal Calcium Sensor-1/D2 Dopamine Receptor Interaction for Antipsychotic Drug Development
Current Drug Targets Antipsychotics and Cognitive Functioning: A Critical Review
Current Psychopharmacology Multi- and Inter-Disciplinary Science in Personalized Delivery of Stem Cells for Tissue Repair
Current Stem Cell Research & Therapy Adjunctive Depot Antipsychotic in Treatment-Resistant Schizophrenia
Current Psychopharmacology Alpha-synuclein, Proteotoxicity and Parkinson's Disease: Search for Neuroprotective Therapy
Current Neuropharmacology Chondroitin Sulfate, a Major Niche Substance of Neural Stem Cells, and Cell Transplantation Therapy of Neurodegeneration Combined with Niche Modification
Current Stem Cell Research & Therapy The Role of Oxidative Stress in Huntington’s Disease: Are Antioxidants Good Therapeutic Candidates?
Current Drug Targets mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems
Current Drug Targets Oxidative Stress in the Early Stage of Psychosis
Current Topics in Medicinal Chemistry Xanthine Derivatives as Agents Affecting Non-dopaminergic Neuroprotection in Parkinson’s Disease
Current Medicinal Chemistry Recent Progress in Anticonvulsant Drug Research: Strategies for Anticonvulsant Drug Development and Applications of Antiepileptic Drugs for Non-Epileptic Central Nervous System Disorders
Current Topics in Medicinal Chemistry Memantine and Kynurenic Acid: Current Neuropharmacological Aspects
Current Neuropharmacology Current Therapeutic Options for Alzheimers Disease
Current Genomics Progress in Understanding Basal Ganglia Dysfunction as a Common Target for Methamphetamine Abuse and HIV-1 Neurodegeneration
Current HIV Research Proceedings of the Regional Conference of the International Society for Adolescent Psychiatry and Psychology (ISAPP), a Joint Conference with 18<sup>th</sup> National Symposium of Adolescent Mental Health, Ankara, Turkey, November 21-24, 2013<sup>1</sup>
Adolescent Psychiatry Adenosine in the Central Nervous System: Effects on Neurotransmission and Neuroprotection
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Asthma in Childhood – Making the Diagnosis
Current Pediatric Reviews Thioridazine: The Good and the Bad
Recent Patents on Anti-Infective Drug Discovery Natural Products Combating Neurodegeneration: Parkinson’s Disease
Current Drug Metabolism The Treatment of Behavioral and Psychological Symptoms of Dementia: Weighing Benefits and Risks
Current Alzheimer Research