Handbook of experimental pharmacology最新文献_第7页

Introduction: A Short History of Adrenoceptor Research. 导言：肾上腺素受体研究简史。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_718

Martin C Michel

引用次数: 0

Genetic Variants of Adrenoceptors. 肾上腺素受体的遗传变异。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_676

Andrea Ahles, Stefan Engelhardt

{"title":"Genetic Variants of Adrenoceptors.","authors":"Andrea Ahles, Stefan Engelhardt","doi":"10.1007/164_2023_676","DOIUrl":"10.1007/164_2023_676","url":null,"abstract":"Adrenoceptors are class A G-protein-coupled receptors grouped into three families (α1-, α2-, and β-adrenoceptors), each one including three members. All nine corresponding adrenoceptor genes display genetic variation in their coding and adjacent non-coding genomic region. Coding variants, i.e., nucleotide exchanges within the transcribed and translated receptor sequence, may result in a difference in amino acid sequence thus altering receptor function and signaling. Such variants have been intensely studied in vitro in overexpression systems and addressed in candidate-gene studies for distinct clinical parameters. In recent years, large cohorts were analyzed in genome-wide association studies (GWAS), where variants are detected as significant in context with specific traits. These studies identified two of the in-depth characterized 18 coding variants in adrenoceptors as repeatedly statistically significant genetic risk factors - p.Arg389Gly in the β1- and p.Thr164Ile in the β2-adrenoceptor, along with 56 variants in the non-coding regions adjacent to the adrenoceptor gene loci, the functional role of which is largely unknown at present. This chapter summarizes current knowledge on the two coding variants in adrenoceptors that have been consistently validated in GWAS and provides a prospective overview on the numerous non-coding variants more recently attributed to adrenoceptor gene loci.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"27-54"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Biophysical and Pharmacological Insights to CLC Chloride Channels. 对 CLC 氯化通道的生物物理和药理认识。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2022_594

Hwoi Chan Kwon, Robert H Fairclough, Tsung-Yu Chen

{"title":"Biophysical and Pharmacological Insights to CLC Chloride Channels.","authors":"Hwoi Chan Kwon, Robert H Fairclough, Tsung-Yu Chen","doi":"10.1007/164_2022_594","DOIUrl":"10.1007/164_2022_594","url":null,"abstract":"The CLC family encompasses two functional categories of transmembrane proteins: chloride conducting channels and proton-chloride antiporters. All members in this chloride channel/transporter family consist of two identical protein subunits, and each subunit forms an independent ion-transport pathway, a structural architecture known as \"double barrel.\" These CLC proteins serve biological functions ranging from membrane excitability and cell volume regulation to acidification of endosomes. Despite their ubiquitous expression, physiological significance, and resolved molecular structures of some of the family members, the mechanisms governing these molecules' biophysical functions are still not completely settled. However, a series of functional and structural studies have brought insights into interesting questions related to these proteins. This chapter explores the functional peculiarities underlying CLC channels aided by information observed from the chloride-proton antiporters in the CLC family. The overall structural features of these CLC proteins will be presented, and the biophysical functions will be addressed. Finally, the mechanism of pharmacological agents that interact with CLC channels will also be discussed.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"1-34"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovation at the Interface between Academia and Industry: The BioMed X Model. 学术界与产业界之间的创新：生物医学 X 模型。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_729

Flavia-Bianca Cristian, Christian Tidona, Thomas Rückle

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Regulatory Aspects for Approval of Advanced Therapy Medicinal Products in the EU. 欧盟先进治疗药物产品审批的监管问题。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_648

Shayesteh Fürst-Ladani, Anja Bührer, Walter Fürst, Nathalie Schober-Ladani

{"title":"Regulatory Aspects for Approval of Advanced Therapy Medicinal Products in the EU.","authors":"Shayesteh Fürst-Ladani, Anja Bührer, Walter Fürst, Nathalie Schober-Ladani","doi":"10.1007/164_2023_648","DOIUrl":"10.1007/164_2023_648","url":null,"abstract":"In the European Union (EU), advanced therapy medicinal products (ATMPs) undergo evaluation by the European Medicines Agency's (EMA) Committee for Advanced Therapies (CAT) to obtain marketing authorization under the centralized procedure. Because of the diversity and complexity of ATMPs, a tailored approach to the regulatory process is required that needs to ensure the safety and efficacy of each product. Since ATMPs often target serious diseases with unmet medical need, the industry and authorities are interested in providing treatment to patients in a timely manner through optimized and expedited regulatory pathways. EU legislators and regulators have implemented various instruments to support the development and authorization of innovative medicines by offering scientific guidance at early stages, incentives for small developers and products for rare diseases, accelerated evaluation of marketing authorization applications, different types of marketing authorizations, and tailored programs for medicinal products with the orphan drug designation (ODD) and the Priority Medicines (PRIME) scheme. Since the regulatory framework for ATMPs was established, 20 products have been licenced, 15 with orphan drug designation, and 7 supported by PRIME. This chapter discusses the specific regulatory framework for ATMPs in the EU and highlights previous successes and remaining challenges.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"367-387"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9302620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Presynaptic Adrenoceptors. 突触前肾上腺素受体。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_714

Bela Szabo

{"title":"Presynaptic Adrenoceptors.","authors":"Bela Szabo","doi":"10.1007/164_2024_714","DOIUrl":"10.1007/164_2024_714","url":null,"abstract":"Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. β2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"185-245"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206. 体积调节阴离子通道 VRAC/LRRC8 和质子激活氯离子通道 ASOR/TMEM206 的生理功能

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_673

Yulia Kostritskaia, Malte Klüssendorf, Yingzhou Edward Pan, Fatemeh Hassani Nia, Simona Kostova, Tobias Stauber

{"title":"Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.","authors":"Yulia Kostritskaia, Malte Klüssendorf, Yingzhou Edward Pan, Fatemeh Hassani Nia, Simona Kostova, Tobias Stauber","doi":"10.1007/164_2023_673","DOIUrl":"10.1007/164_2023_673","url":null,"abstract":"Volume-regulated anion channels (VRACs) and the acid-sensitive outwardly rectifying anion channel (ASOR) mediate flux of chloride and small organic anions. Although known for a long time, they were only recently identified at the molecular level. VRACs are heteromers consisting of LRRC8 proteins A to E. Combining the essential LRRC8A with different LRRC8 paralogues changes key properties of VRAC such as conductance or substrate selectivity, which is how VRACs are involved in multiple physiological functions including regulatory volume decrease, cell proliferation and migration, cell death, purinergic signalling, fat and glucose metabolism, insulin signalling, and spermiogenesis. VRACs are also involved in pathological conditions, such as the neurotoxic release of glutamate and aspartate. Certain VRACs are also permeable to larger, organic anions, including antibiotics and anti-cancer drugs, making them an interesting therapeutic target. ASOR, also named proton-activated chloride channel (PAC), is formed by TMEM206 homotrimers on the plasma membrane and on endosomal compartments where it mediates chloride flux in response to extracytosolic acidification and plays a role in the shrinking and maturation of macropinosomes. ASOR has been shown to underlie neuronal swelling which causes cell death after stroke as well as promoting the metastasis of certain cancers, making them intriguing therapeutic targets as well.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"181-218"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From Innovator Result-driven to Multi-actor Impact-oriented Public-Private Partnerships: Integrating the Patient Perspective. 从创新成果驱动型公私合作伙伴关系到多行为体影响导向型公私合作伙伴关系：整合患者视角。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_730

R L A de Vrueh, J S B de Vlieger, K M Orrling, J M L van Rensen

{"title":"From Innovator Result-driven to Multi-actor Impact-oriented Public-Private Partnerships: Integrating the Patient Perspective.","authors":"R L A de Vrueh, J S B de Vlieger, K M Orrling, J M L van Rensen","doi":"10.1007/164_2024_730","DOIUrl":"10.1007/164_2024_730","url":null,"abstract":"Public-Private Partnerships (PPPs) have been crucial in medicine research and development (R&D) for decades. Initially, PPPs involved private and academic innovators working in bilateral collaborations to advance pharmaceutical innovation. Later, a precompetitive open innovation environment was created, where multiple public and private innovators collaborated on mutual interests. The entry of regulators and patient interest organizations into PPPs has triggered a third shift from an innovator result-driven to a multi-actor impact-oriented partnership model. Using the second Innovative Medicines Initiative program (IMI2) as an example, this chapter focuses on the increasing roles of patient interest organizations in PPPs in roughly the last decade.Most IMI2 partnerships focused on raising awareness and sharing information tailored to patient needs (listener role) and inviting patients to share their experiences and needs (co-thinker role). Many partnerships also integrated the patient perspective by implementing patient advisory bodies (advisor role) or including patients as equal partners in steering the project (partner role). Notably, partnerships like EUPATI and PARADIGM showed that patient interest organizations can lead initiatives, especially those aiming at advancing patient engagement across the medicine R&D lifecycle (decision-maker role). While the overall impact of patient involvement in the IMI2 program is still being assessed, it has exposed many innovators and regulators to the patient perspective and created a community of patient experts with access to tools and guidelines for meaningful involvement.The PPP model continues to evolve, shifting from a treatment-only to a comprehensive diagnosis, treatment, and monitoring approach by incorporating digital and medical technology actors. This development, alongside continued patient and public integration could revolutionize the R&D and accessibility of new treatments and diagnostics.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"137-168"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biodegradable Long-Acting Injectables: Platform Technology and Industrial Challenges. 生物降解长效注射剂：平台技术与工业挑战。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_651

Marieta Duvnjak, Alessia Villois, Farshad Ramazani

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Sustainability in Drug and Nanoparticle Processing. 药物和纳米粒子加工的可持续性。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_659

Dagmar Fischer

{"title":"Sustainability in Drug and Nanoparticle Processing.","authors":"Dagmar Fischer","doi":"10.1007/164_2023_659","DOIUrl":"10.1007/164_2023_659","url":null,"abstract":"The formulation of drugs in poly(lactic-co-glycolic acid) (PLGA) nanoparticles can be accomplished by various methods, with nanoprecipitation and nanoemulsion being among the most commonly used manufacturing techniques to provide access to high-quality nanomaterials with reproducible quality. Current trends turned to sustainability and green concepts leading to a re-thinking of these techniques, particularly as the conventional solvents for the dissolution of the polymer suffer from limitations like hazards for human health and natural environment. This chapter gives an overview about the different excipients used in classical nanoformulations with a special focus on the currently applied organic solvents. As alternatives, the status quo of green, sustainable, and alternative solvents regarding their application, advantages, and limitations will be highlighted as well as the role of physicochemical solvent characteristics like water miscibility, viscosity, and vapor pressure for the selection of the formulation process, and for particle characteristics. New alternative solvents will be introduced for PLGA nanoparticle formation and compared regarding particle characteristics and biological effects as well as for in situ particle formation in a matrix consisting of nanocellulose. Conclusively, new alternative solvents are available that present a significant advancement toward the replacement of organic solvents in PLGA nanoparticle formulations.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"45-68"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0