Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

10.1124/pr.117.014647

2018-04-01

Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contri...

Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption

10.1124/pr.117.014407

2018-04-01

Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for dec...

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

10.1124/pr.117.014753

2018-04-01

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)–like...

Etiology and Pharmacology of Neuropathic Pain

10.1124/pr.117.014399

2018-04-01

Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, and time-dependent processes, including neuroimmune interactions at the peripheral, supraspinal, and spinal levels, contri...

Drugs for Insomnia beyond Benzodiazepines: Pharmacology, Clinical Applications, and Discovery

10.1124/pr.117.014381

2018-04-01

Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon di...

Biomarkers for In Vivo Assessment of Transporter Function

10.1124/pr.116.013326

2018-04-01

Drug–drug interactions are a major concern not only during clinical practice, but also in drug development. Due to limitations of in vitro–in vivo predictions of transporter-mediated drug–drug interactions, multiple clinical Phase I drug–drug interaction stud...

International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function

10.1124/pr.116.013177

2018-01-01

Chemerin, a chemoattractant protein and adipokine, has been identified as the endogenous ligand for a G protein–coupled receptor encoded by the gene CMKLR1 (also known as ChemR23), and as a consequence the receptor protein was renamed the chemerin receptor in...

Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies

10.1124/pr.117.014456

2018-01-01

Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching—from precise diagnosis and classif...

WNT Signaling in Cardiac and Vascular Disease

10.1124/pr.117.013896

2018-01-01

WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterni...

G Protein–Coupled Receptors Targeting Insulin Resistance, Obesity, and Type 2 Diabetes Mellitus

10.1124/pr.117.014373

2018-01-01

G protein–coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in the development of insulin resistance and β-cell dysfunction, and in the etiology of infla...