结构-组织暴露/选择性关系 (STR) 关于大麻二醇的碳酸盐
Sheng Wang1, Jian-Guo Yang1, Kuanrong Rong1
1Center for Scientific Research, School of Pharmacy, Anhui Medical University, Hefei 230032, China.
International journal of molecular sciences
|November 27, 2024
概括
结构-组织暴露/选择性关系 (STR) 影响药物的有效性和安全性. 修改大麻二醇碳酸盐改变了组织暴露,证明了STR.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- 结构-组织暴露/选择性关系 (STR) 对于优化候选药物,平衡剂量,疗效和毒性至关重要.
- 二醇 (CBD) 碳酸盐向胆固醇化酶 (BuChE) 用于研究与疗效和毒性相关的STR.
研究的目的:
- 探索STR与使用新型CBD碳酸盐观察到的疗效/毒性之间的相关性.
- 了解结构修改如何影响药物的药理动力学,组织暴露和选择性.
主要方法:
- 合成和评估具有不同结构的CBD碳酸盐.
- 用于评估血和大脑暴露的药理动力学研究.
- 组织暴露/选择性和疗效/安全概况之间的相关性分析.
- 评估碳酸盐功能组的代谢稳定性.
主要成果:
- 具有相似结构和标的CBD碳酸盐表现出各种各样的药理动力学特征.
- 血暴露L2和L4是相似的,但不能预测大脑暴露;然而,组织暴露/选择性与疗效/安全相关.
- 在CBD碳酸盐中的结构变化调节了血和组织暴露/选择性.
- 二级氨基碳酸盐被代谢成CBD,而三级氨基酸则显示出更大的稳定性.
结论:
- 通过改变正常组织中的组织暴露,STR显著影响药物的有效性和安全性.
- 吸收,分布,新陈代谢,分泌和毒性 (ADMET) 参数可以预测STR.
- 平衡结构-活性关系 (SAR) 和STR对于成功优化候选药物和改善临床试验结果至关重要.
相关概念视频
Chemotherapy-Induced Nausea and Vomiting: Cannabinoids
202
Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
Two synthetic agonists of THC,...
Two synthetic agonists of THC,...
202
Dose-Response Relationship: Selectivity and Specificity
6.5K
Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and...
6.5K
Tissue-Drug Binding: Localization of Drugs and its Significance
67
Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine...
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine...
67
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
163
CNS stimulants, such as cocaine, amphetamines, and cannabinoids, have varying structures and mechanisms of action that lead to different therapeutic effects and side effects. Cocaine, with its molecular formula C17H21NO4, is a tropane alkaloid and a tertiary amino compound. It has two chemical forms: the hydrochloride salt and the "freebase." The former is in powder form, while the latter involves removing the hydrochloride salt to create a form that can be smoked. Cocaine exerts its...
163
Structure-Activity Relationships and Drug Design
595
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
595
Dose-Response Relationship: Overview
3.0K
Agonists can bind with and activate receptors, resulting in the formation of drug-receptor complexes. Once formed, these complexes catalyze many biochemical processes at the cellular level and subsequently induce a pharmacologic response. The degree of response is directly proportional to the fraction of activated receptors, which in turn, depends on the concentration of the drug at the receptor site as well as the sensitivity of the receptor. An increase in the administered dose contributes to...
3.0K


