Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, PA 19104, USA.
Future Med Chem. 2009 Aug;1(5):821-33. doi: 10.4155/fmc.09.85.
The use of fluorinated molecules as drugs and imaging agents for CNS disorders has been studied extensively over the years. Incorporating a fluorine atom into the structure of a drug changes its physiochemical properties and can thereby lead to much more desirable pharmacokinetic and pharmacodynamic properties. This change can help to facilitate blood-brain barrier permeability, which is a critical matter for drugs intended for CNS activities. Fluorine incorporation into structures of drugs for the treatment of neurodegenerative diseases has been an attractive field for drug discovery. Such incorporation can greatly influence the physicochemical properties, metabolic stability and receptor binding affinity of the resulting molecule. Some studies have shown that when a proton was substituted with fluorine, the binding or inhibitory potency was greatly increased. The fluorine-18 isotope, (18)F, is utilized in detection and diagnosis of neurodegenerative diseases, whereas (19)F compounds are used in the treatment of these diseases and in MRI. (18)F is widely used in PET imaging because it offers the advantage of a longer half-life compared with other radionuclides. It is used for imaging various receptors and transporters that have been linked to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple system atrophy. Fluorine plays an important role in the diagnosis and treatment of many CNS diseases, including neurodegenerative disorders. The use of fluorine in the diagnosis and treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, will be discussed in this review.
多年来，人们一直在广泛研究将含氟分子作为药物和中枢神经系统（CNS）疾病成像剂的用途。在药物结构中引入氟原子会改变其物理化学性质，从而带来更理想的药代动力学和药效学特性。这种变化有助于促进血脑屏障通透性，这对于旨在作用于中枢神经系统的药物至关重要。将氟原子引入治疗神经退行性疾病的药物结构中一直是药物发现的一个有吸引力的领域。这种引入可以极大地影响所得分子的物理化学性质、代谢稳定性和受体结合亲和力。一些研究表明，当用氟原子取代质子时，结合或抑制效力大大增加。氟-18 同位素（18F）用于检测和诊断神经退行性疾病，而（19）F 化合物则用于治疗这些疾病和磁共振成像（MRI）。（18）F 广泛用于正电子发射断层扫描（PET）成像，因为与其他放射性核素相比，它具有更长的半衰期优势。它用于成像与神经退行性疾病（如阿尔茨海默病、帕金森病、亨廷顿病和多系统萎缩）相关的各种受体和转运体。氟在许多中枢神经系统疾病的诊断和治疗中都起着重要作用，包括神经退行性疾病。本综述将讨论氟在神经退行性疾病（如阿尔茨海默病和帕金森病）的诊断和治疗中的应用。
