Selective small molecule angiotensin II type 2 receptor antagonists for neuropathic pain: preclinical and clinical studies.

摘要: Neuropathic pain affects up to 10% of the general population, but drug treatments recommended for treatment neuropathic are associated with modest efficacy and/or produce dose-limiting side effects. Hence, is an unmet medical need. In past 2 decades, research on pathobiology has revealed many novel targets use in analgesic discovery programs. However, these efforts have been largely unsuccessful as molecules that showed promising relief rodent models generally failed analgesia early phase clinical trials patients pain. One notable exception angiotensin II type (AT2) receptor validity basis a successful double-blind, randomized, placebo-controlled, trial EMA401, highly selective, orally active, peripherally restricted AT2 antagonist postherpetic neuralgia. this study, we review date target validation, efficacy, and mode action small molecule antagonists peripheral cultured human sensory neurons, preclinical pharmacokinetics compounds, outcome above trial.