6- ((3- cyclobutyl- 2,3,4,5- tetrahydro- 1H- 3- benzazepin- 7- yl)oxy)- N- methyl- 3- pyridinecarboxamide

08/15/2008 - "These data suggest that H(3) antagonists such as GSK189254 and GSK334429 may be useful for the treatment of neuropathic pain."
08/15/2008 - "In the present study we investigated the effects of the novel potent and highly selective H(3) receptor antagonists GSK189254 (6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride) and GSK334429 (1-(1-methylethyl)-4-([1-[6-(trifluoromethyl)-3-pyridinyl]-4-piperidinyl]carbonyl)hexahydro-1H-1,4-diazepine) in two rat models of neuropathic pain, namely the chronic constriction injury (CCI) model and the varicella-zoster virus (VZV) model. "
11/18/2022 - "The Histamine H4 Receptor Participates in the Neuropathic Pain-Relieving Activity of the Histamine H3 Receptor Antagonist GSK189254."
08/15/2008 - "Novel histamine H3 receptor antagonists GSK189254 and GSK334429 are efficacious in surgically-induced and virally-induced rat models of neuropathic pain."
10/01/2010 - "GSK189254 also displayed efficacy in a rat surrogate model indicative of central sensitization, namely phase 2 response of formalin-induced flinching, and attenuated tactile allodynia in the spinal nerve ligation model of neuropathic pain (ED(50)=1.5mg/kg i.p.). "

11/18/2022 - "Since H3R and H4R are both localized in neuronal areas devoted to pain processing, the aim of the study is to investigate the role of H4R in the mechanism of anti-hyperalgesic action of the H3R antagonist GSK189254 in the spared nerve injury (SNI) model in mice. "
10/01/2010 - "In the present study, the effects of GSK189254, a potent and selective H(3) antagonist, were characterized in preclinical pain models in rats. "
10/01/2010 - "When administered intrathecally (i.t.) to the lumbar spinal cord, GSK189254 produced robust effects in relieving the OA pain (ED(50)=0.0027 mg/kg i.t.). "
10/01/2010 - "Systemic GSK189254 produced dose-dependent efficacy (ED(50)=0.77 mg/kg i.p.) in a rat model of monoiodoacetate (MIA) induced osteoarthritic (OA) pain as evaluated by hindlimb grip force. "
08/15/2008 - "Specific binding to H(3) receptors was demonstrated with [(3)H]-GSK189254 in the dorsal horn of the human and rat spinal cord, and in human dorsal root ganglion (DRG), consistent with the potential involvement of H(3) receptors in pain processing. "

01/01/2022 - "Positron emission tomography (PET) studies with the radiolabeled potent and selective histamine H3 receptor antagonist [11C]GSK-189254 in rodents could be used to examine the mechanisms of action of novel therapeutic drugs or to assess changes of regional H3 receptor density in animal models of neurodegenerative disease. "

10/01/2012 - "After oral administration of JNJ-39220675 (1 mg/kg), the fractional receptor occupancy was >0.9 at 90 min with a slight increase from 90 to 240 min. Similar to prior studies in humans, V (T) was highly sensitive to the mass of GSK189254 with ED(50) estimated to be 0.16 μg/kg. The robust blockade of binding of [(11)C]GSK189254 by JNJ-39220675 demonstrates that this compound readily penetrates the blood-brain barrier and occupies the histamine H(3) receptor after oral administration at low plasma concentrations (∼1 ng/cc) supporting further drug development for alcohol addiction and other disorders. "

05/01/2009 - "However, within the AD group, [3H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death. "
06/01/2007 - "These data suggest that GSK189254 may have therapeutic potential for the symptomatic treatment of dementia in Alzheimer's disease and other cognitive disorders."
12/15/2013 - "This Letter describes the discovery of GSK189254 and GSK239512 that were progressed as clinical candidates to explore the potential of H3 receptor antagonists as novel therapies for the treatment of Alzheimer's disease and other dementias. "