pf-04455242 has been researched along with Pain* in 2 studies
1 review(s) available for pf-04455242 and Pain
| Article | Year |
|---|---|
Selective kappa opioid antagonists for treatment of addiction, are we there yet?
Kappa opioid receptor (KOP) is a G-protein coupled receptor mainly expressed in the cerebral cortex and hypothalamus. It is implicated in nociception, diuresis, emotion, cognition, and immune system functions. KOP agonists possess a strong analgesic effect accompanied by a feeling of dysphoria. On the other hand, antagonists of this receptor were found to block depression, anxiety, and drug-seeking behaviors in animal models. Recently, great interest has been given to the development of selective KOP antagonists as an addiction treatment that does not cause dependence itself or show high relapse rates like the currently used agents. This review provides a comprehensive survey of the KOP antagonists developed for this purpose together with their in vivo studies and clinical trials. In addition, a future perspective and recommendations for the work needed to develop clinically relevant KOP antagonists are presented. Topics: Animals; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Receptors, Opioid, kappa | 2017 |
1 other study(ies) available for pf-04455242 and Pain
| Article | Year |
|---|---|
Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).
By use of parallel chemistry coupled with physicochemical property design, a series of selective κ opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro κ antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the κ K(i) and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Area Under Curve; Biphenyl Compounds; Brain; Disease Models, Animal; Dogs; Drug Design; Drug Discovery; Haplorhini; Humans; Metabolic Clearance Rate; Mice; Microsomes, Liver; Models, Chemical; Molecular Structure; Morphine; Narcotic Antagonists; Pain; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Structure-Activity Relationship; Sulfonamides | 2011 |