RESUMEN
OBJECTIVE: The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism. MATERIALS AND METHODS: This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia with moderate or greater pain received TV-45070 and placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared with the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted. RESULTS: Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed). CONCLUSIONS: The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation.
Asunto(s)
Indoles/uso terapéutico , Canal de Sodio Activado por Voltaje NAV1.7/genética , Neuralgia Posherpética/tratamiento farmacológico , Neuralgia Posherpética/genética , Bloqueadores de los Canales de Sodio/uso terapéutico , Compuestos de Espiro/uso terapéutico , Administración Tópica , Estudios Cruzados , Femenino , Genotipo , Humanos , Indoles/efectos adversos , Indoles/sangre , Masculino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Bloqueadores de los Canales de Sodio/efectos adversos , Bloqueadores de los Canales de Sodio/sangre , Compuestos de Espiro/efectos adversos , Compuestos de Espiro/sangre , Resultado del TratamientoAsunto(s)
Intoxicación por Ciguatera/diagnóstico , Trastornos Neurológicos de la Marcha/etiología , Alimentos Marinos/efectos adversos , Animales , Canadá/etnología , Chile , Intoxicación por Ciguatera/fisiopatología , Ciguatoxinas/efectos adversos , Ciguatoxinas/química , Dinoflagelados/química , Etanol/efectos adversos , Femenino , Peces , Humanos , Paris , Recurrencia , Bloqueadores de los Canales de Sodio/efectos adversos , Bloqueadores de los Canales de Sodio/química , Viaje , Adulto JovenRESUMEN
Scorpion venom toxins generally produce similar effects by mainly acting on sodium channels, and to a lesser extent, on potassium, calcium, and chloride channels. This leads to increased release of neurotransmitters and mediators, resulting in a cascade of pathological events, involving the central nervous system, the autonomic nervous system, the cardiovascular and the respiratory system, eventually leading to death. The objective of this paper was to discover whether a sodium channel blocker, lidocaine, or a calcium channel blocker, verapamil, would prolong the survival of mice injected with the venom from the common yellow scorpion Leiurus quinquestriatus quinquestriatus (LQQ). For this purpose, mice were divided into 2 groups, each injected with a different venom dose (250 or 300 µg.kg-1, s.c.). Subgroups (n=10) from each group were given venom alone; different doses of lidocaine (4, 10, 15, or 20 mg.kg-1); or several doses of verapamil (0.01, 0.03, 0.1, 0.3, or 1 mg.kg-1). All doses of lidocaine and verapamil were intravenously administered 3 minutes before, 1, 5, and 15 minutes after venom injection. Percent surviving after 24 hours was recorded in addition to the time of death. In general, lidocaine significantly prolonged survival at the dose of 10 mg.kg-1 (P<0.05 and P<0.01, versus low and high dose of venom, respectively) or 15 mg.kg-1 (P<0.01 and P<0.001, versus low and high dose of venom, respectively; Covariance Wilcoxon survival statistics), especially when injected before the venom or in the early stages of envenomation. On the other hand, in all doses administered, verapamil was either toxic or showed non-significant results. Lidocaine, the sodium channel blocker, appears to play an important role in the protection from lethality of mice injected with LQQ venom, and significantly prolonged the survival time of mice whether injected before or in the early stages of envenomation.(AU)