Journal of Medicinal Chemistry · 2007 · 15 citations · 27 references
MedicineNeurosciencePharmacologyNeurochemistryNeuropharmacologyPain MedicineAnalgesiaNeurochemical PharmacologyNeuropathic Pain PharmacotherapyPain NeurobiologyPain NeurosciencePharmacologic Pain TherapyAqueous Solubility ImprovementAqueous Solubility OptimizationNmda Receptor AntagonismNmda Receptor AntagonistsNociceptive Pain PharmacotherapyOral Drug BioavailabilityPain PharmacologyPharmacological Pain Relief
A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally.
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A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Kenneth Hargreaves, Ronald Dubner, Frederick J. Brown et al. · Pain · 1988 · 5.2K citations