RESUMO
Eleven compounds belonging to the chalcone family were tested for their ability to activate and subsequently desensitize the rat transient receptor potential ankyrin 1 cation channel, subfamily A, member 1 (TRPA1) in a heterologous expression system. Four of the tested compounds were more potent than the TRPA1 agonist mustard oil, and showed also a strong desensitizing effect. Some chalcone compounds were not pungent in the eye-wiping assay and quite remarkably inhibited in a long-lasting and dose-dependent manner the pain response in the formalin test. Chalcones can be considered as novel candidates for the development of antihyperalgesic preparations based on TRPA1 desensitization.
Assuntos
Analgésicos/química , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Chalconas/uso terapêutico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Anti-Inflamatórios/química , Cálcio/metabolismo , Chalconas/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Formaldeído/toxicidade , Células HEK293 , Humanos , Inflamação/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mostardeira/toxicidade , Dor/induzido quimicamente , Medição da Dor , Óleos de Plantas/toxicidade , Ratos , Relação Estrutura-Atividade , Canal de Cátion TRPA1 , Canais de Potencial de Receptor Transitório/químicaRESUMO
Although used for more than 4000 years for recreational and medicinal purposes, Cannabis and its best-known pharmacologically active constituents, the cannabinoids, became a protagonist in medical research only recently. This revival of interest is explained by the finding in the 1990s of the mechanism of action of the main psychotropic cannabinoid, Delta9-tetrahydrocannabinol (THC), which acts through specific membrane receptors, the cannabinoid receptors. The molecular characterization of these receptors allowed the development of synthetic molecules with cannabinoid and noncannabinoid structure and with higher selectivity, metabolic stability, and efficacy than THC, as well as the development of antagonists that have already found pharmaceutical application. The finding of endogenous agonists at these receptors, the endocannabinoids, opened new therapeutic possibilities through the modulation of the activity of cannabinoid receptors by targeting the biochemical mechanisms controlling endocannabinoid tissue levels.