digoxin has been researched along with Neuralgia* in 2 studies
2 other study(ies) available for digoxin and Neuralgia
| Article | Year |
|---|---|
Discovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain.
Effective treatment of chronic pain, in particular neuropathic pain, without the side effects that often accompany currently available treatment options is an area of significant unmet medical need. A phenotypic screen of mouse gene knockouts led to the discovery that adaptor protein 2-associated kinase 1 (AAK1) is a potential therapeutic target for neuropathic pain. The synthesis and optimization of structure-activity relationships of a series of aryl amide-based AAK1 inhibitors led to the identification of Topics: Amides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain; Caco-2 Cells; Dose-Response Relationship, Drug; Drug Discovery; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Microsomes, Liver; Molecular Structure; Neuralgia; Protein Kinases; Protein Serine-Threonine Kinases; Structure-Activity Relationship | 2021 |
Characterization of thien-2-yl 1S,2R-milnacipran analogues as potent norepinephrine/serotonin transporter inhibitors for the treatment of neuropathic pain.
Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than 1S,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration. Topics: Administration, Oral; Animals; Biological Availability; Caco-2 Cells; Crystallography, X-Ray; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Humans; Male; Microsomes, Liver; Milnacipran; Models, Molecular; Molecular Structure; Molecular Weight; Neuralgia; Norepinephrine Plasma Membrane Transport Proteins; Pain Measurement; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Spinal Nerves; Stereoisomerism; Structure-Activity Relationship | 2008 |