RESUMO
A new iridoid glucoside, sesinoside (1), was isolated from the seedlings of Sesamum indicum. The structure of 1 was elucidated by spectroscopic analyses and by methanolysis of 1, which produced the known compounds, phlorigidosides C (2) and (6Z)-foliamenthic acid methyl ester (3). This is the first report of an iridoid glucoside with 3.
Assuntos
Glucosídeos Iridoides/química , Plântula/química , Sesamum/química , Estrutura MolecularRESUMO
A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expressing human TRPV1. The most potent of these TRPV1 antagonists were further characterized in pharmacokinetic, efficacy, and body temperature studies. On the basis of its pharmacokinetic, in vivo efficacy, safety, and toxicological properties, compound 37 was selected for further evaluation in human clinical trials.
Assuntos
Aminopiridinas/química , Analgésicos/química , Dor/tratamento farmacológico , Canais de Cátion TRPV/antagonistas & inibidores , Aminopiridinas/farmacocinética , Aminopiridinas/farmacologia , Analgésicos/farmacocinética , Analgésicos/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Células CHO , Cálcio/metabolismo , Capsaicina/farmacologia , Cricetulus , Adjuvante de Freund , Gânglios Espinais/citologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Dor/etiologia , Ratos Sprague-Dawley , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/fisiologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Thirteen patients with metastatic colorectal cancer who suffered from oxaliplatin-induced sensory neuropathy were evaluated to determine the neuropathy Grade before and after the administration of pregabalin. All patients received oxaliplatin as adjuvant or first-line chemotherapy. The mFOLFOX6 and CapeOX groups included 3 and 10 cases, respectively, and the average treatment regimens were 8 and 5 doses, respectively. Before receiving pregabalin, sensory neuropathy was classified as Grade 3 in 2 patients, as Grade 2 in 8 patients, and as Grade 1 in 3 patient. The average amount of pregabalin administered to patients was 237 (range: 150-450) mg. After administering pregabalin, we observed improvements in 8 neuropathy cases (61. 5%)within approximately 2 weeks. All side effects were mild. In this study, pregabalin was shown to positively impact sensory neuropathy resulting from oxaliplatin treatment and to enable the long-term use of oxaliplatin-based chemotherapy.