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The development of medications to treat cocaine use disorders has thus far defied success, leaving this patient population without pharmacotherapeutic options. As the dopamine transporter (DAT) plays a prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and based on its pharmacological profile, the lead compound 10a was evaluated in phase I metabolic stability studies in mouse liver microsomes and compared to cocaine in locomotor activity and drug discrimination paradigms in mice. A molecular dynamic simulation study supported the hypothesis that atypical DAT inhibitors have similar binding poses at DAT in a conformation that differs from that of cocaine. Such differences may ultimately contribute to their unique behavioral profiles and potential for development as cocaine use disorder therapeutics.
This article was published in the following journal.
Name: Journal of medicinal chemistry
The glycoside hydrolase family 4 (GH4) α-galactosidase from Citrobacter Freundii (MelA) catalyzes the hydrolysis of fluoro-substituted phenyl α-D-galactopyranosides by utilizing two cofactors, NAD a...
1,2,4-Triazole derivatives containing a piperazine nucleus (4a-d and 10) were prepared starting from 1-(2-methoxyphenyl)piperazine or ethyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate via sever...
Multiple drug resistance (MDR) is one major barrier in cancer management, urging for new drugs to help treat MDR malignancies and elucidate MDR mechanisms. A series of chromene compounds (CXL series) ...
Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery.
Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to t...
Inhibition of α-glucosidase is an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. For the identification of new inhibitors of this enzyme, a series of new (R)...
The purpose of this study is to explore the effects of genes and genetic variation on brain structure and function. Investigators at Harvard plan to explore the relationship between candid...
This study is designed to evaluate the relationship between diaphragm activity during mechanical ventilation and the development of ventilator-induced diaphragm dysfunction (VIDD). Diaphra...
The nutritional quality of foods strongly depends on the structure / texture of foods, because of the impact on food disintegration, and then on digestion process and nutrient utilization ...
To assess the relationship of community socioeconomic (SE) structure to cardiovascular disease and all-cause mortality trends in the United States.
Previous research studies have shown that depression is associated with changes in structure and activity in different parts of the brain and that antidepressant medication can affect brai...
A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
An application that must be submitted to a regulatory agency (the FDA in the United States) before a drug can be studied in humans. This application includes results of previous experiments; how, where, and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in animal studies; and how the compound is manufactured. (From the "New Medicines in Development" Series produced by the Pharmaceutical Manufacturers Association and published irregularly.)
A spectroscopic technique which uses the Mossbauer effect (inelastic scattering of gamma radiation resulting from interaction with heavy nuclei) to monitor the small variations in the interaction between an atomic nucleus and its environment. Such variations may be induced by changes in temperature, pressure, chemical state, molecular conformation, molecular interaction, or physical site. It is particularly useful for studies of structure-activity relationship in metalloproteins, mobility of heavy metals, and the state of whole tissue and cell membranes.
Psychiatry is the study of mental disorders and their diagnosis, management and prevention. Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...