Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
1.
J Behav Health Serv Res ; 49(3): 406-413, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35001257

RESUMEN

The novel coronavirus (SARS-CoV-2 or COVID19) has defied the healthcare system at every turn. The impact of this pandemic on ensuring the health and safety of individuals with serious and persistent mental illness-particularly those living in community-based residential settings-has been challenging. As one of the largest community behavioral health organizations in Oregon, the authors present a descriptive study of an organizational response to the COVID-19 pandemic. This paper presents barriers, strategies, and lessons learned, through firsthand experience and interviews with key residential staff. This paper is not formal research, but the integration and assessment of staff perspective, and organizational experience and knowledge. By sharing these insights and experience, this paper contributes to a collective roadmap for the future, to guide responses to public health crises or other unprecedented events that threaten organizations caring for some of the most vulnerable members of the community.


Asunto(s)
COVID-19 , Trastornos Mentales , Atención a la Salud , Humanos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Pandemias , SARS-CoV-2
2.
J Pain Symptom Manage ; 60(3): 595-601.e3, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32376264

RESUMEN

OBJECTIVES: To determine how demographic, socioeconomic, health, and psychosocial factors predict preferences to accept life-prolonging treatments (LPTs) at the end of life (EOL). METHODS: This is a retrospective cohort study of a nationally representative sample of community-dwelling older Americans (N = 1648). Acceptance of LPT was defined as wanting to receive all LPTs in the hypothetical event of severe disability or severe chronic pain at the EOL. Participants with a durable power of attorney, living will, or who discussed EOL with family were determined to have expressed their EOL preferences. The primary analysis used survey-weighted logistic regression to measure the association between older adult characteristics and acceptance of LPT. Secondarily, the associations between LPT preferences and health outcomes were measured using regression models. RESULTS: Approximately 31% of older adults would accept LPT. Nonwhite race/ethnicity (odds ratio [OR] 0.54; 95% CI 0.41, 0.70; white vs. nonwhite), self-realization (OR 1.34; 95% CI 1.01, 1.79), attendance of religious services (OR 1.44; 95% CI 1.07, 1.94), and expression of preferences (OR 0.54; 95% CI 0.40, 0.72) were associated with acceptance of LPT. LPT preferences were not independently associated with mortality or disability. CONCLUSIONS: Approximately one-third of older Americans would accept LPT in the setting of severe disability or severe chronic pain at the EOL. Adults who discussed their EOL preferences were more likely to reject LPT. Conversely, minorities were more likely to accept LPT. Sociodemographics, physical capacity, and health status were poor predictors of acceptance of LPT. A better understanding of the complexities of LPT preferences is important to ensuring patient-centered care.


Asunto(s)
Vida Independiente , Cuidado Terminal , Anciano , Muerte , Humanos , Voluntad en Vida , Estudios Retrospectivos , Estados Unidos
4.
Disabil Rehabil ; 41(2): 191-200, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29117730

RESUMEN

BACKGROUND: The built, social and economic environments are associated with disability, but knowledge of how these environmental characteristics simultaneously influence older adults' ability to shop independently is limited. OBJECTIVE: We investigated cross-sectional associations between the outdoor home, local neighborhood and macrosocioeconomic levels of the environment and shopping difficulty and interactions between environmental factors and shopping difficulty. METHODS: Using nationally representative data from a study of Medicare-eligible adults, we conducted a cross-sectional secondary data analysis to examine associations between the environment and difficulty shopping (N = 5504). RESULTS: Sidewalk conditions, broken steps, neighborhood social cohesion and neighborhood socioeconomic disadvantage were associated with more difficulty shopping, although health factors partially accounted for associations between broken steps and disadvantage and shopping difficulty. The association between social cohesion and shopping difficulty also depended on the degree of socioeconomic disadvantage in the neighborhood. CONCLUSIONS: Overall, results suggest that factors in the outdoor and local neighborhood environment influence the ability to shop independently for older adults, but that it also may depend on the socioeconomic context of the neighborhood. Interventions aimed at improving the built environment directly outside of older adults' homes and helping increase social cohesion among neighbors, has the potential to reduce difficulty in carrying out this important activity. Implications for rehabilitation Built features of the outdoor home environment including sidewalks and broken steps influence whether older adults are able to safely leave their home to conduct daily activities such as shopping, so it is important that clinicians and rehabilitation professionals are aware of these challenges when helping their patients resume daily activities such as shopping. The physical condition and safety of the immediate outdoor home and neighborhood environment is critical for maintaining independence and well-being for older adults, which is critical for physical rehabilitation as well as maintenance of essential activities such as shopping. Living in more socially cohesive neighborhoods may aid in physical rehabilitation efforts by helping older adults feel more comfortable and able to shop independently in neighborhoods with social and economic disadvantages.


Asunto(s)
Actividades Cotidianas/psicología , Vida Independiente , Mercadotecnía , Características de la Residencia , Anciano , Redes Comunitarias/organización & administración , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Vida Independiente/psicología , Vida Independiente/normas , Relaciones Interpersonales , Masculino , Mercadotecnía/métodos , Mercadotecnía/normas , Evaluación de Necesidades , Apoyo Social , Factores Socioeconómicos , Estados Unidos
5.
J Racial Ethn Health Disparities ; 5(5): 978-994, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29218498

RESUMEN

Differences in coping within the African American population are not well understood, yet these differences may be critical to reducing stress, improving health, and reducing racial health disparities. Using a descriptive, exploratory analysis of the Jackson Heart Study (N = 5301), we examine correlations between coping responses and associations between coping and demographic, socioeconomic, psychosocial, and neighborhood factors. Overall, coping responses were not strongly correlated and patterns of associations between covariates and coping responses were largely inconsistent. The results suggest that coping varies substantially within this African American population and is driven mainly by psychosocial factors such as spirituality and interpersonal support. Understanding these complex relationships may inform strategies by which to intervene in the stress process to mitigate the effects of stress on health and to identify vulnerable subgroups of African Americans that might need targeted interventions to reduce exposure to stressors and improve coping capacities.


Asunto(s)
Adaptación Psicológica , Negro o Afroamericano/psicología , Racismo/psicología , Estrés Psicológico/psicología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Depresión/psicología , Emociones , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Optimismo/psicología , Solución de Problemas , Religión , Apoyo Social , Adulto Joven
6.
Psychosom Med ; 80(2): 184-192, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29215456

RESUMEN

OBJECTIVE: A long-hypothesized pathway through which low socioeconomic status (SES) harms health is through dysregulation of the physiologic stress response systems. No previous studies have tested this hypothesis by investigating cortisol reactivity and recovery to acute stress in relation to SES at different times in the life course in adults. Alteration of the cortisol response to an acute stressor could signal dysregulation of the hypothalamic-pituitary-adrenal axis and has been associated with chronic illness. METHODS: We used data on 997 adults 54 years or older from a multiethnic, multisite United States study to examine associations between life course SES and cortisol response to a laboratory stress challenge. Informed by life course theory, we hypothesized that lower child and adult SES would be associated with lower reactivity (i.e., smaller increase in cortisol) and a slower recovery rate (i.e., slower rate of decline in cortisol after the challenge). RESULTS: In demographics-adjusted multilevel piecewise linear regression models, low child and adult SES were associated with a 19% (95% CI = 4%-50%) and 27% (7%-55%) slower recovery rate compared with high child and adult SES, respectively. Compared with participants with stable high SES, those with stable low SES had a 48% (16%-70%) slower recovery rate. Differences in reactivity by SES were small. CONCLUSIONS: Our results support the hypothesis that low SES throughout life affects the hypothalamic-pituitary-adrenal axis and in turn the ability to recover from exposure to acute stressors. This mechanism can help explain how socioeconomic disparities contribute to disparities in chronic disease.


Asunto(s)
Adultos Sobrevivientes de Eventos Adversos Infantiles , Hidrocortisona/metabolismo , Estrés Psicológico/metabolismo , Anciano , Aterosclerosis/etnología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Saliva , Clase Social , Estrés Psicológico/etnología , Estados Unidos/etnología
7.
Res Aging ; 40(2): 103-130, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-27909061

RESUMEN

Our understanding of the mechanisms through which racial/ethnic disparities in disability in older adults develop and are maintained is limited. We examined the role of physical impairment, socioeconomic factors and health for racial/ethnic disparities in activities of daily living (ADL), and the modifying role of the indoor home environment. Data come from the National Health and Aging Trends Study ( N = 5,640), and negative binomial regression models were specified separately for men and women. Blacks and Hispanics reported more ADL difficulty than Whites. Living in homes with clutter was associated with higher rates of ADL difficulty, but it was not related to racial/ethnic disparities. Racial/ethnic differences were explained by physical impairment for men, but not for women. Socioeconomic factors and health accounted for remaining disparities for Black, but not for Hispanic women. Attention to individual and environmental factors is necessary to fully understand and address race/ethnic disparities in disability in older Americans.


Asunto(s)
Actividades Cotidianas , Personas con Discapacidad , Etnicidad , Disparidades en el Estado de Salud , Grupos Raciales , Medio Social , Anciano , Humanos , Análisis de Regresión , Factores Sexuales , Factores Socioeconómicos , Estados Unidos
8.
J Aging Health ; 30(1): 75-104, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-27605555

RESUMEN

OBJECTIVES: We test a comprehensive model of disability in older stroke survivors and determine the relative contribution of neighborhood, economic, psychological, and medical factors to disability. METHOD: The sample consisted of 728 stroke survivors from the National Health and Aging Trends Study (NHATS), who were 65 years and older living in community settings or residential care. Confirmatory factor analysis and structural equation modeling were used to test relationships between neighborhood, socioeconomic, psychological, and medical factors, and disability. RESULTS: Economic and medical context were associated with disability directly and indirectly through physical impairment. Neighborhood context was associated with disability, but was only marginally statistically significant ( p = .05). The effect of economic and neighborhood factors was small compared with that of medical factors. DISCUSSION: Neighborhood and economic factors account for a portion of the variance in disability among older stroke survivors beyond that of medical factors.


Asunto(s)
Personas con Discapacidad , Rendimiento Físico Funcional , Características de la Residencia , Accidente Cerebrovascular/psicología , Sobrevivientes , Anciano , Evaluación de la Discapacidad , Personas con Discapacidad/psicología , Personas con Discapacidad/rehabilitación , Femenino , Humanos , Vida Independiente/estadística & datos numéricos , Masculino , Evaluación de Necesidades , Instituciones Residenciales/estadística & datos numéricos , Factores Socioeconómicos , Sobrevivientes/psicología , Sobrevivientes/estadística & datos numéricos
9.
SSM Popul Health ; 2: 798-806, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28584861

RESUMEN

PURPOSE: Mental health is critical to young adult health, as the onset of 75% of psychiatric disorders occurs by age 24 and psychiatric disorders early in life predict later behavioral health problems. Wealth may serve as a buffer against economic stressors. Family wealth may be particularly relevant for young adults by providing them with economic resources as they make educational decisions and move towards financial and social independence. METHODS: We used prospectively collected data from 2060 young adults aged 18-27 in 2005-2011 from the Panel Study of Income Dynamics, a national cohort of US families. We examined associations between nonspecific psychological distress (measured with the K-6 scale) and childhood average household wealth during ages 0-18 years (net worth in 2010 dollars). RESULTS: In demographics-adjusted generalized estimating equation models, higher childhood wealth percentile was related to a lower prevalence of serious psychological distress: compared to below-median wealth, prevalence ratio (PR) = 0.56 (0.36-0.87) for 3rd quartile and PR = 0.46 (0.29-0.73) for 4th quartile. The associations were attenuated slightly by adjustment for parent education and more so by adjustment for childhood household income percentile. CONCLUSIONS: Understanding the lifelong processes through which distinct aspects of socioeconomic status affect mental health can help us identify high-risk populations and take steps to minimize future disparities in mental illness.

10.
Subst Use Misuse ; 50(12): 1606-17, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26579610

RESUMEN

BACKGROUND: Living in neighborhoods with a high density of alcohol outlets and socioeconomic disadvantage may increase residents' alcohol use. Few researchers have studied these exposures in relation to multiple types of alcohol use, including beverage-specific consumption, and how individual demographic factors influence these relationships. OBJECTIVE: To examine the relationships of alcohol outlet density and neighborhood disadvantage with alcohol consumption, and to investigate differences in these associations by race/ethnicity and income. METHODS: Using cross-sectional data (N = 5,873) from the Multi-ethnic Study of Atherosclerosis in 2002, we examine associations of residential alcohol outlet density and neighborhood socioeconomic disadvantage with current, total weekly and heaviest daily alcohol use in gender-specific regression models, as well as moderation by race/ethnicity and income. RESULTS: Drinking men living near high densities of alcohol outlets had 23%-29% more weekly alcohol use than men in low density areas. Among women who drank, those living near a moderate density of alcohol outlets consumed approximately 40% less liquor each week than those in low density areas, but higher outlet densities were associated with more wine consumption (35%-49%). Living in highly or moderately disadvantaged neighborhoods was associated with a lower probability of being a current drinker, but with higher rates of weekly beer consumption. Income moderated the relationship between neighborhood context and weekly alcohol use. CONCLUSIONS/IMPORTANCE: Neighborhood disadvantage and alcohol outlet density may influence alcohol use with effects varying by gender and income. Results from this research may help target interventions and policy to groups most at risk for greater weekly consumption.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas/provisión & distribución , Renta/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Clase Social , Anciano , Anciano de 80 o más Años , Bebidas Alcohólicas/estadística & datos numéricos , Cerveza/estadística & datos numéricos , Cerveza/provisión & distribución , Comercio/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores Socioeconómicos , Estados Unidos/epidemiología , Vino/estadística & datos numéricos , Vino/provisión & distribución
11.
Soc Sci Med ; 145: 17-25, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26439763

RESUMEN

Neighborhood socioeconomic characteristics and alcohol availability may affect alcohol consumption, but adequate longitudinal research to support these hypotheses does not exist. We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6163) to examine associations of changes in neighborhood socioeconomic status (SES) and alcohol outlet density, with current, weekly, and heavy daily alcohol consumption in hybrid effects models. We also examined whether these associations were moderated by gender, race/ethnicity, and income. Increases in neighborhood SES were associated with decreases in the probability of current alcohol use after adjustment for age, gender, race/ethnicity, individual SES, marital status and time since baseline [probability ratio (PR) per SD increase in neighborhood SES = 0.96, 95% confidence interval (CI) (0.96.0.99)]. Increases in liquor store densities were associated with increases in weekly alcohol consumption [ratio of weekly drinks per SD increase in outlet density = 1.07, 95% CI (1.01.1.05) for men, PR = 1.11, 95% CI (1.01.1.21) for women]. Relationships between current alcohol use and neighborhood SES and between weekly beer consumption and neighborhood SES were generally stronger among those with higher incomes. Neighborhood socioeconomic context and the availability of alcohol may be important for understanding patterns of alcohol use over time, and for targeting interventions and policies to reduce harmful alcohol use.


Asunto(s)
Consumo de Bebidas Alcohólicas/economía , Características de la Residencia , Factores Socioeconómicos , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/etnología , Aterosclerosis/etnología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Clase Social , Estados Unidos
12.
Violence Vict ; 30(4): 649-62, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26159914

RESUMEN

The positive association between alcohol outlet density and assault rates is well established, but little is known about how this association differs across victim subpopulations. We use spatial point process models on police data from Flint, Michigan, to test how the link between alcohol outlet density and assault rates changes as a function of three victim characteristics: age, gender, and race. We found that, although both on-premises and package outlet densities consistently emerge as risk factors for victimization, their relative effects are markedly larger in Whites than in African Americans. No analogous age- or gender-based differences were found. These results suggest the racial effects arise more from relative differences in the atmosphere in and around alcohol outlets than differences in drinking behavior alone.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Bebidas Alcohólicas/provisión & distribución , Comercio/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Violencia/estadística & datos numéricos , Algoritmos , Femenino , Humanos , Masculino , Michigan/epidemiología , Modelos Estadísticos
13.
J Am Heart Assoc ; 4(6): e001553, 2015 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-26019130

RESUMEN

BACKGROUND: Few studies have examined the impact of lifecourse socioeconomic position (SEP) on cardiovascular disease (CVD) risk among African Americans. METHODS AND RESULTS: We used data from the Jackson Heart Study (JHS) to examine the associations of multiple measures of lifecourse SEP with CVD events in a large cohort of African Americans. During a median of 7.2-year follow-up, 362 new or recurrent CVD events occurred in a sample of 5301 participants aged 21 to 94. Childhood SEP was assessed by using mother's education, parental home ownership, and childhood amenities. Adult SEP was assessed by using education, income, wealth, and public assistance. Adult SEP was more consistently associated with CVD risk in women than in men: age-adjusted hazard ratios for low versus high income (95% CIs), 2.46 (1.19 to 5.09) in women and 1.50 (0.87 to 2.58) in men, P for interaction=0.1244, and hazard ratio for low versus high wealth, 2.14 (1.39 to 3.29) in women and 1.06 (0.62 to 1.81) in men, P for interaction=0.0224. After simultaneous adjustment for all adult SEP measures, wealth remained a significant predictor of CVD events in women (HR=1.73 [1.04, 2.85] for low versus high). Education and public assistance were less consistently associated with CVD. Adult SEP was a stronger predictor of CVD events in younger than in older participants (HR for high versus low summary adult SEP score 3.28 [1.43, 7.53] for participants ≤50 years, and 1.90 (1.36 to 2.66) for participants >50 years, P for interaction 0.0846). Childhood SEP was not associated with CVD risk in women or men. CONCLUSIONS: Adult SEP is an important predictor of CVD events in African American women and in younger African Americans. Childhood SEP was not associated with CVD events in this population.


Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Enfermedades Cardiovasculares/etnología , Clase Social , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto Joven
14.
Am J Community Psychol ; 51(3-4): 544-56, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23400396

RESUMEN

We examine the association between neighborhood socio-economic disadvantage and perceived stress during middle and late adolescence among African American youth (N = 665; 51 % female; M = 15.9 years at baseline). In addition, we explored the ways through which neighborhood stressors interacted with an individual's intra- and interpersonal resources (e.g., coping, social support and substance use), to affect their perceived stress trajectories during adolescence. First, we tested a neighborhood stressors model and found that youth who lived in neighborhoods with greater socioeconomic disadvantage had higher baseline stress and a steeper increase in stress over time. When we included individual-level risk and promotive factors in the model, however, the effect of neighborhood disadvantage on perceived stress was no longer significant, and the stress trajectory was explained by adolescent substance use, social support and perceptions of the neighborhood. Our results support theories of stress and coping, and the importance of proximal intra- and interpersonal factors in either amplifying or mitigating perceptions of stress. We discuss implications of the neighborhood context and how our findings may inform future prevention and intervention related to adolescent stress and development.


Asunto(s)
Adaptación Psicológica , Relaciones Interpersonales , Modelos Teóricos , Características de la Residencia , Estrés Psicológico/etnología , Adolescente , Negro o Afroamericano , Femenino , Humanos , Masculino , Michigan/epidemiología , Áreas de Pobreza , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios
15.
J Youth Adolesc ; 42(6): 792-806, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23086016

RESUMEN

Evidence suggests that the consequences of chronic exposure to stressors extend beyond psychological effects, and that adolescents living in socio-economically disadvantaged neighborhoods may experience an accumulation of exposure to stressors that wears down the physical systems in the body, resulting in hyper-activation of the stress response. This research examines the relationship between exposure to neighborhood stressors and salivary cortisol reactivity in a sample of 163 at-risk African American adolescents (average age 21; 50% female) living in disadvantaged urban neighborhoods. More specifically, the relationship between neighborhood stressors and physiological stress, measured by baseline cortisol and cortisol reactivity is assessed. This research also examines several moderating pathways between exposure to neighborhood disadvantage and cortisol reactivity including substance use, high effort coping, psychological stress and social support. Results indicate that both individual and neighborhood-level factors influence adolescent cortisol. High effort coping and psychological stress were associated with cortisol in the sample, and exposure to neighborhood socio-economic disadvantage resulted in an atypical cortisol response. In addition, neighborhood disadvantage interacted with intra- and interpersonal factors to affect cortisol indirectly. Thus, living in disadvantaged neighborhoods may take a psychological and physiological toll on adolescents, and it also may exert synergistic effects through individual coping and vulnerabilities.


Asunto(s)
Adaptación Psicológica/fisiología , Hidrocortisona/metabolismo , Pobreza/psicología , Características de la Residencia , Saliva/química , Estrés Psicológico/fisiopatología , Adolescente , Negro o Afroamericano , Femenino , Humanos , Masculino , Apoyo Social , Factores Socioeconómicos
16.
J Stud Alcohol Drugs ; 72(4): 651-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21683047

RESUMEN

OBJECTIVE: Risk factors for adolescent alcohol use are typically conceptualized as individual and interpersonal level factors; however, these factors do not fully explain adolescent drinking behavior. We used a socioecological model to examine the contribution of neighborhood factors in a risk and promotive model of adolescent alcohol use among urban high school youth (N = 711; 52% female; 82% African American; M = 18 years old). METHOD: Using a multilevel model, we considered the role of neighborhood disadvantage on youth alcohol use, after accounting for risk (e.g., peer and parental substance use) and promotive factors (e.g., social support and participation in prosocial activities). RESULTS: Peer alcohol use and peer support were associated with more alcohol use, and maternal support was negatively associated with alcohol use. Despite significant variation at the neighborhood level, neighborhood disadvantage was not directly associated with adolescent drinking. CONCLUSIONS: Our study contributes to a mixed body of literature on social context and adolescent health. Although our research highlights the importance of interpersonal relationships, we found no support for neighborhood influences. We conclude with future directions for research examining the link between adolescent drinking and neighborhood contexts.


Asunto(s)
Consumo de Bebidas Alcohólicas/tendencias , Anomia (Social) , Características de la Residencia , Medio Social , Adolescente , Conducta del Adolescente , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Depresores del Sistema Nervioso Central/efectos adversos , Bases de Datos Factuales , Etanol/efectos adversos , Femenino , Humanos , Relaciones Interpersonales , Masculino , Padres , Grupo Paritario , Grupos Raciales , Factores de Riesgo , Instituciones Académicas , Estudiantes , Trastornos Relacionados con Sustancias/psicología , Población Urbana
17.
Bioorg Med Chem Lett ; 20(12): 3579-83, 2010 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-20483614

RESUMEN

A series of 5-arylamino-1,2,4-triazin-6(1H)-ones was synthesized and evaluated as antagonists at the corticotropin releasing factor receptor. Formation of CYP-mediated oxidative reactive metabolites previously observed in a related N(3)-phenylpyrazinone structure was minimized by incorporation of the additional ring nitrogen found in the triazinones.


Asunto(s)
Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Triazinas/síntesis química , Triazinas/farmacología , Animales , Humanos , Concentración 50 Inhibidora , Oxidación-Reducción , Pirazinas , Ratas , Relación Estructura-Actividad
18.
J Med Chem ; 52(14): 4161-72, 2009 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-19552436

RESUMEN

A series of pyrazinone-based heterocycles was identified as potent and orally active corticotropin-releasing factor-1 (CRF(1)) receptor antagonists. Selected compounds proved efficacious in an anxiety model in rats; however, pharmacokinetic properties were not optimal. In this article, we describe an in vitro intrinsic clearance-based approach to the optimization of pyrazinone-based CRF(1) receptor antagonists wherein sites of metabolism were identified by incubation with human liver microsomes. It was found that the rate of metabolism could be decreased by incorporation of appropriate substituents at the primary sites of metabolism. This led to the discovery of compound 12x, a highly potent (IC(50) = 1.0 nM) and selective CRF(1) receptor antagonist with good oral bioavailability (F = 52%) in rats and efficacy in the defensive withdrawal anxiety test in rats.


Asunto(s)
Pirazinas/farmacología , Pirazinas/farmacocinética , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Animales , Humanos , Concentración 50 Inhibidora , Masculino , Tasa de Depuración Metabólica , Pirazinas/química , Pirazinas/metabolismo , Ratas , Receptores de Hormona Liberadora de Corticotropina/metabolismo
19.
J Med Chem ; 52(14): 4173-91, 2009 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-19552437

RESUMEN

Evidence suggests that corticotropin-releasing factor-1 (CRF(1)) receptor antagonists may offer therapeutic potential for the treatment of diseases associated with elevated levels of CRF such as anxiety and depression. A pyrazinone-based chemotype of CRF(1) receptor antagonists was discovered. Structure-activity relationship studies led to the identification of numerous potent analogues including 12p, a highly potent and selective CRF(1) receptor antagonist with an IC(50) value of 0.26 nM. The pharmacokinetic properties of 12p were assessed in rats and Cynomolgus monkeys. Compound 12p was efficacious in the defensive withdrawal test (an animal model of anxiety) in rats. The synthesis, structure-activity relationships and in vivo properties of compounds within the pyrazinone chemotype are described.


Asunto(s)
Pirazinas/química , Pirazinas/farmacología , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Animales , Línea Celular Tumoral , Humanos , Macaca fascicularis , Masculino , Pirazinas/síntesis química , Pirazinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad
20.
Bioorg Med Chem Lett ; 15(6): 1619-21, 2005 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15745809

RESUMEN

A series of N,N-dimethylhomotryptamines was prepared and their binding affinities at the serotonin transporter (SERT) were determined. Compounds possessing an electron withdrawing substituent at the C5-position of the indole nucleus were found to be potent SSRIs. Initial attempts at conformational restriction of the propylamine sidechain by incorporation of a quinuclidine bicyclic structure did not improve binding affinity at SERT.


Asunto(s)
Inhibidores Selectivos de la Recaptación de Serotonina/química , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Triptaminas/química , Triptaminas/farmacología , Línea Celular , Humanos , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Modelos Químicos , Estructura Molecular , Proteínas del Tejido Nervioso/metabolismo , Unión Proteica , Proteínas de Transporte de Serotonina en la Membrana Plasmática
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA