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1.
J Addict Med ; 18(3): 274-281, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426533

RESUMO

OBJECTIVE: The medical community has become aware of its role in contributing to the opioid epidemic and must be part of its resolution. Recovery community centers (RCCs) represent a new underused component of recovery support. METHODS: This study performed an online national survey of all RCCs identified in the United States, and used US Census ZIP code tabulation area data to describe the communities they serve. RESULTS: Residents of areas with RCCs were more likely to be Black (16.5% vs 12.6% nationally, P = 0.005) and less likely to be Asian (4.7% vs 5.7%, P = 0.005), American Indian, or Alaskan Native (0.6% vs 0.8%, P = 0.03), or live rurally (8.5% vs 14.0%, P < 0.0001). More than half of RCCs began operations within the past 5 years. Recovery community centers were operated, on average, by 8.8 paid and 10.2 volunteer staff; each RCC served a median of 125 individuals per month (4-1,500). Recovery community centers successfully engaged racial/ethnic minority groups (20.8% Hispanic, 22.5% Black) and young adults (23.5% younger than 25 years). Recovery community centers provide addiction-specific support (eg, mutual help, recovery coaching) and assistance with basic needs, social services, technology access, and health behaviors. Regarding medications for opioid use disorder (MOUDs), RCC staff engaged members in conversations about MOUDs (85.2%) and provided direct support for taking MOUD (77.0%). One third (36.1%) of RCCs reported seeking closer collaboration with prescribers. CONCLUSIONS: Recovery community centers are welcoming environments for people who take MOUDs. Closer collaboration between the medical community and community-based peer-led RCCs may lead to significantly improved reach of efforts to end the opioid epidemic.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Humanos , Estados Unidos , Adulto , Masculino , Transtornos Relacionados ao Uso de Opioides/reabilitação , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Feminino , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Pessoa de Meia-Idade
2.
Bioorg Med Chem ; 27(23): 115096, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629610

RESUMO

FAAH inhibitors offer safety advantages by augmenting the anandamide levels "on demand" to promote neuroprotective mechanisms without the adverse psychotropic effects usually seen with direct and chronic activation of the CB1 receptor. FAAH is an enzyme implicated in the hydrolysis of the endocannabinoid N-arachidonoylethanolamine (AEA), which is a partial agonist of the CB1 receptor. Herein, we report the discovery of a new series of highly potent and selective carbamate FAAH inhibitors and their evaluation for neuroprotection. The new inhibitors showed potent nanomolar inhibitory activity against human recombinant and purified rat FAAH, were selective (>1000-fold) against serine hydrolases MGL and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Evaluation of FAAH inhibitors 9 and 31 using the in vitro competitive activity-based protein profiling (ABPP) assay confirmed that both inhibitors were highly selective for FAAH in the brain, since none of the other FP-reactive serine hydrolases in this tissue were inhibited by these agents. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on known FAAH cocrystal structures. To rationally design new molecules that are irreversibly bound to FAAH, we have constructed "precovalent" FAAH-ligand complexes to identify good binding geometries of the ligands within the binding pocket of FAAH and then calculated covalent docking poses to select compounds for synthesis. FAAH inhibitors 9 and 31 were evaluated for neuroprotection in rat hippocampal slice cultures. In the brain tissue, both inhibitors displayed protection against synaptic deterioration produced by kainic acid-induced excitotoxicity. Thus, the resultant compounds produced through rational design are providing early leads for developing therapeutics against seizure-related damage associated with a variety of disorders.


Assuntos
Amidoidrolases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Fármacos Neuroprotetores/farmacologia , Piperazina/farmacologia , Piperidinas/farmacologia , Amidoidrolases/metabolismo , Animais , Desenho de Fármacos , Inibidores Enzimáticos/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Piperazina/análogos & derivados , Piperidinas/química , Ratos
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