RESUMO
Mobile applications represent an immense opportunity to support and improve patient health care, as the scope and functionality of medical apps are enabling physicians and patients to manage care in new, fast, and personalized ways. Several challenges exist in medical-app development, including careful attention to quality systems, medical-device regulation, and app life span. Despite these complexities, we find that development of mobile medical apps is a worthwhile undertaking given their potential to improve outcomes for patients.
Assuntos
Telefone Celular , Atenção à Saúde/normas , Aplicativos Móveis , Assistência ao Paciente/métodos , Humanos , Indústrias/tendências , Legislação de Dispositivos Médicos , Assistência ao Paciente/normas , Médicos/normas , Medicina de Precisão/métodos , Software , Fatores de TempoRESUMO
The tachykinins, substance P, neurokinin A, and neurokinin B, have been implicated in many diseases. The present study evaluated the pharmacological properties of a novel tachykinin antagonist ZD6021 [3-cyano-N-((2S)-2-(3,4-dichlorophenyl)-4-[4-[2-(methyl-(S)-sulfinyl)-phenyl]piperidino]butyl)-N-methyl-]-napthamide]. The affinity (K(i)) of ZD6021 for the cloned human neurokinin (NK)1, NK2, and NK3 receptors was 0.12 +/- 0.01, 0.64 +/- 0.08, and 74 +/- 13 nM, respectively. Mucin secretion by Chinese hamster ovary cells transfected with the human NK1 receptor was dose dependently inhibited by ZD6021: pIC(50) = 7.6 +/- 0.1. For NK1 and NK2 receptors, the agonist concentration-response curves using isolated tissues were displaced rightward in the presence of ZD6021: rabbit pulmonary artery, pA2 = 8.7 and 8.5; human pulmonary artery and bronchus, pKB = 8.9 +/- 0.4 and 7.5 +/- 0.2, at 10(-7) M, respectively. Senktide-induced contractions of isolated guinea pig ileum were also blocked by low concentrations of ZD6021. Oral administration of ZD6021 to guinea pigs dose dependently attenuated tracheal extravasation of plasma proteins induced by the NK1 receptor agonist Ac-[Arg6,Sar9,Met(O2)11]-SP(6-11), ED50 = 0.8 micromol/kg, and bronchoconstriction, elicited by the NK2 receptor agonist [beta-Ala8]-NKA(4-10), ED50 = 20 micromol/kg. Potency was unaffected by feeding. After oral administration of ZD6021, the time to peak activity was 150 min for the NK1 receptor and 60 min for the NK2 receptor with pharmacodynamic half-lives of 280 and 458 min, respectively. These data indicate that ZD6021 is a potent, orally active antagonist of all three tachykinin receptors. This compound may be useful for future studies of tachykinin-related pathology such as asthma.
Assuntos
Broncoconstrição/efeitos dos fármacos , Íleo/efeitos dos fármacos , Antagonistas dos Receptores de Neurocinina-1 , Artéria Pulmonar/efeitos dos fármacos , Receptores da Neurocinina-2/antagonistas & inibidores , Receptores da Neurocinina-3/antagonistas & inibidores , Substância P/análogos & derivados , Administração Oral , Animais , Cricetinae , Cobaias , Humanos , Íleo/fisiologia , Masculino , Fragmentos de Peptídeos/farmacologia , Piperidinas/farmacologia , Artéria Pulmonar/fisiologia , Coelhos , Receptores da Neurocinina-1/metabolismo , Receptores da Neurocinina-2/metabolismo , Receptores da Neurocinina-3/metabolismo , Receptores de Taquicininas/antagonistas & inibidores , Receptores de Taquicininas/metabolismo , Substância P/farmacologia , Sulfóxidos/farmacologiaRESUMO
Endothelin-1 (ET-1) is a potent vasoconstrictor and comitogen implicated in the pathogenesis of pulmonary hypertension (PH). We evaluated the effects of an ET(A)receptor-selective antagonist, ZD1611, on hypoxia-induced PH in rats. <