RESUMEN
Considering the lengthy history of pharmacological treatment of schizophrenia, the development of novel antipsychotic agents targeting the glutamatergic system is relatively new. A glutamatergic deficit has been proposed to underlie many of the symptoms typically observed in schizophrenia, particularly the negative and cognitive symptoms (which are less likely to respond to current treatments). D-serine is an important coagonist of the glutamate NMDA receptor, and accumulating evidence suggests that D-serine levels and/or activity may be dysfunctional in schizophrenia and that facilitation of D-serine transmission could provide a significant therapeutic breakthrough, especially where conventional treatments have fallen short. A summary of the relevant animal data, as well as genetic studies and clinical trials examining D-serine as an adjunct to standard antipsychotic therapy, is provided in this article. Together, the evidence suggests that research on the next generation of antipsychotic agents should include studies on increasing brain levels of D-serine or mimicking its action on the NMDA receptor.
Asunto(s)
Antipsicóticos/farmacología , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Serina/metabolismo , Serina/farmacología , Animales , Humanos , Esquizofrenia/fisiopatologíaRESUMEN
Panic disorder has been associated with both an increased risk of coronary events as well as an increased risk of stroke. Hemoconcentration, with both a decrease in plasma volume and an increase in plasma viscosity, is a possible contributor to the risk of acute ischemic events. Our objectives were to demonstrate the process of hemoconcentration in response to induced panic symptoms and to assess the effect of pretreatment with ethinyl estradiol on panic-induced hemoconcentration. Fifteen male patients with panic disorder and 10 male healthy volunteers were included in a double-blind cross-over placebo-controlled design consisting of two injections of pentagastrin following randomized pretreatment with placebo and ethinyl estradiol. Plasma levels of hematocrit and hemoglobin were assessed at baseline and post-injections, and used to calculate an indirect estimation of the change in plasma volume. Pentagastrin-induced panic symptoms were associated with a mean decrease in plasma volume of 4.8% in the placebo pretreatment condition. Pretreatment with ethinyl estradiol attenuated this effect. The acute hemoconcentration observed in relation to pentagastrin-induced panic symptoms may be relevant to the increased risk of stroke and acute coronary events found in patients with panic disorder.
Asunto(s)
Viscosidad Sanguínea/efectos de los fármacos , Estrógenos/farmacología , Etinilestradiol/farmacología , Trastorno de Pánico/sangre , Pánico/efectos de los fármacos , Pentagastrina/efectos adversos , Volumen Plasmático/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Estrógenos/administración & dosificación , Etinilestradiol/administración & dosificación , Hematócrito , Hemoglobinas/análisis , Humanos , Masculino , Pentagastrina/farmacología , Escalas de Valoración PsiquiátricaRESUMEN
OBJECTIVE: Panic disorder (PD) has been associated with an increased risk for cardiovascular (CV) morbidity and mortality. There are inconsistent reports of increased low-density lipoprotein cholesterol (LDL-C) in patients with PD. Studies have reported a correlation between cholesterol levels and the intensity and frequency of panic attacks (PAs), suggesting that an elevation in cholesterol could be due to physiological and neurochemical changes that occur during and after a PA. The objective of our study was to show that the occurrence of a PA is associated with an increase in LDL-C. MATERIALS AND METHODS: We used a double-blind, placebo-controlled crossover design with randomized injections of placebo and pentagastrin in 18 patients with PD (11 men, 7 women) and 33 healthy-control subjects (24 men, 9 women). RESULTS: Pentagastrin-induced PAs were associated with a statistically significant 10.4% delayed (24 h) increase in LDL-C levels in male subjects. Such an effect was not observed in female subjects. CONCLUSION: LDL-C levels are directly affected by the occurrence of a PA in males. These findings, in association with previous reports of increased cholesterol levels in PD patients, suggest that a chronic increase in LDL-C as a result of frequent PAs may be one of the mechanisms that contributes, at least in male patients, to previously reported increased CV risk in patients with PD. The gender difference and the temporal association between PAs and increased LDL-C may explain the inconsistency in the findings of previous investigations of cholesterol levels in PD patients.
Asunto(s)
LDL-Colesterol/sangre , Trastorno de Pánico/sangre , Pentagastrina/efectos adversos , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Trastorno de Pánico/inducido químicamenteRESUMEN
The herpes simplex virus virion host shutoff protein (vhs) is an mRNA-specific RNase that contributes to shutoff of host protein synthesis. We show here that vhs-induced mRNA decay proceeds 5' to 3' in an in vitro assay system derived from rabbit reticulocyte lysate.