RESUMO
Eating disorders are associated with impaired decision-making and dysfunctional reward-related neurochemistry. The present study examined the potential contributions of dopamine and opioid signaling to these processes using two different decision-making tasks. In one task, Long Evans Rats chose between working for a preferred food (high-carbohydrate banana-flavored sucrose pellets) by lever pressing on a progressive-ratio schedule of reinforcement vs. obtaining less preferred laboratory chow that was concurrently available. In a second (effort-free) task, rats chose between the same two reinforcers when they were both available freely. Rats were trained in these tasks before receiving haloperidol (0.00, 0.05, 0.10mg/kg, intraperitoneally (i.p.)) or naloxone (0.0, 1.5, 3.0mg/kg, i.p.). In the first task, haloperidol decreased breakpoint, lever presses, number of reinforcers earned, and increased chow intake, whereas naloxone decreased breakpoint and number of reinforcers earned but had no effect on chow consumption. In the effort-free task, haloperidol reduced intakes of both foods without affecting preference, whereas naloxone selectively reduced the consumption of banana-pellets. The present findings support converging evidence suggesting that DA signaling affects processes more closely related to appetitive motivation, leaving other components of motivation unchanged. By contrast, opioid signaling appears to mediate aspects of hedonic feeding by selectively altering intakes of highly palatable foods. For preferred foods, both appetitive and consummatory aspects of food intake were altered by opioid receptor antagonism. Our findings argue against a general suppression of appetite by either compound, as appetite manipulations have been shown to unselectively alter intakes of both types of food regardless of the task employed.
Assuntos
Tomada de Decisões/fisiologia , Dopamina/metabolismo , Comportamento Alimentar/fisiologia , Motivação/fisiologia , Receptores Opioides/metabolismo , Animais , Apetite/efeitos dos fármacos , Apetite/fisiologia , Tomada de Decisões/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Haloperidol/farmacologia , Masculino , Motivação/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos Long-Evans , Receptores Dopaminérgicos/metabolismo , Reforço Psicológico , Percepção Gustatória/efeitos dos fármacos , Percepção Gustatória/fisiologiaRESUMO
CONTEXT: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress. OBJECTIVE: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two-solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized. METHODS: (1) The organic solution containing quinine, a model of bitter compound and poorly water-soluble polymers and (2) sugar alcohol (mannitol) aqueous solution were separately flown in tubes and two solutions were spray dried through two-solution type spray nozzle to prepare polymer-blended quinine nanocomposite particles. Mean diameters of nanoparticles, taste-masking effect and dissolution rate of quinine were evaluated. RESULTS: The results of taste masking by taste sensor suggested that the polymer (Eudragit EPO, Eudragit S100 or Ethyl cellulose)-blended quinine nanocomposite particles exhibited marked masking of instrumental quinine bitterness compared with the quinine nanocomposite particles alone. Quinine nanocomposite formulations altered the quinine dissolution rate, indicating that they can control intestinal absorption of quinine. CONCLUSION: These results suggest that polymer-blended quinine composite particles prepared using our spray-drying technique are useful for masking bitter tastes in the field of food and pharmaceutical industry.
Assuntos
Nanocompostos/química , Polímeros/química , Quinina/química , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Química Farmacêutica/métodos , Dessecação/métodos , Manitol/química , Nanopartículas/química , Tamanho da Partícula , Solubilidade , Soluções/química , Tecnologia Farmacêutica/métodos , Água/químicaRESUMO
CONTEXT: Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. OBJECTIVE: The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. METHODS AND MATERIALS: The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. RESULTS AND DISCUSSION: Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. CONCLUSION: The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.
Assuntos
Sistemas de Liberação de Medicamentos , Excipientes/administração & dosagem , Ácido Glicirrízico/administração & dosagem , Indanos/administração & dosagem , Nootrópicos/administração & dosagem , Piperidinas/administração & dosagem , Edulcorantes/administração & dosagem , Adulto , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/economia , Donepezila , Método Duplo-Cego , Composição de Medicamentos , Custos de Medicamentos , Sistemas de Liberação de Medicamentos/efeitos adversos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Excipientes/química , Excipientes/economia , Ácido Glicirrízico/química , Ácido Glicirrízico/economia , Dureza , Humanos , Indanos/efeitos adversos , Indanos/análise , Indanos/economia , Mucosa Bucal/efeitos dos fármacos , Nootrópicos/efeitos adversos , Nootrópicos/análise , Nootrópicos/economia , Preferência do Paciente , Piperidinas/efeitos adversos , Piperidinas/análise , Piperidinas/economia , Salvia/química , Edulcorantes/química , Edulcorantes/economia , Comprimidos , Paladar , Percepção Gustatória/efeitos dos fármacosRESUMO
We purified several hundred mgs of four major theaflavins (theaflavin, theaflavin-3-O-gallate, theaflavin-3'-O-gallate, and theaflavin-3,3'-O-digallate). Among the 25 hTAS2Rs expressed in HEK293T cells, hTAS2R39 and hTAS2R14 were activated by theaflavins. Both hTAS2R39 and hTAS2R14 responded to theaflavin-3'-O-gallate. In addition, hTAS2R39 was activated by theaflavin and theaflavin-3,3'-O-gallate, but not by theaflavin-3-O-gallate. In contrast, hTAS2R14 responded to theaflavin-3-O-gallate.
Assuntos
Biflavonoides/metabolismo , Biflavonoides/farmacologia , Catequina/metabolismo , Catequina/farmacologia , Receptores de Superfície Celular/metabolismo , Percepção Gustatória/efeitos dos fármacos , Cálcio/metabolismo , Células HEK293 , HumanosRESUMO
Approaches to improve the taste of oral dosage forms that contain unpleasant tasting drugs are versatile. Likewise, the analytical in vitro and in vivo methods to assess taste-masking efficacy are diverse. Taste-masking has gained in importance since the EU legislation on medicines for children came into force in 2007, and taste-masking attributes are often required by regulatory authorities. However, standardized guidance for the analytical evaluation is still poor. Published protocols rarely consider real conditions, such as the volume of saliva or the residence time of solid oral dosage forms in the mouth. Methodological limitations and problems regarding time point of evaluation, sampling or sample pretreatment are hardly ever addressed. This critical review aims to evaluate and discuss published strategies in this context.
Assuntos
Aromatizantes/administração & dosagem , Mascaramento Perceptivo , Preparações Farmacêuticas/administração & dosagem , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Tecnologia Farmacêutica/métodos , Administração Oral , Animais , Técnicas Biossensoriais , Química Farmacêutica , Guias como Assunto , Humanos , Espectrofotometria Ultravioleta , Tecnologia Farmacêutica/normasRESUMO
Taste intensity to 6-n-propylthiouracil (PROP) has been demonstrated to affect food acceptance and food intake. Because most PROP status research has been performed among predominantly white subjects, research is needed to test the effects of PROP taste intensity on food acceptance and body weight among racial minorities. This study was conducted to examine racial differences in the effect of PROP taste intensity and food liking on body mass index between African Americans and Asian Americans. A cross-sectional design with a sample of 50 African Americans (25 women, 25 men) and 50 Asian Americans (23 women, 27 men) in the New York City area aged 18 to 55 years was used in this study. Weight and height were measured and PROP intensity was assessed using PROP filter paper disks. Subjects rated the intensity of 171.15 g/L (0.5 mol/L) sucrose, 29.22 g/L (0.5 mol/L) sodium chloride, 4.8 g/L (0.025 mol/L) citric acid, and 0.127 g/L (3.2×10â»4 mol/L) quinine solutions and completed a questionnaire to report their food liking/disliking for 19 food items. Characteristics were compared using analysis of variance or χ² test. A multiple linear regression model was fit with the covariates PROP mean, race, sex, age, fat-foods liking, and sweet-foods liking to predict body mass index score. The proportion of total nontasters was 22%. There were no significant differences in the PROP status distribution between African Americans and Asian Americans and in food likings between tasters and nontasters. Significant differences in fat foods, sugar, and black coffee liking were observed among the subracial groups (ie, African Caribbean, African black, East Asian, and South Asian). Race, sex, and age significantly contributed to predict body mass index score.
Assuntos
Preferências Alimentares , Variação Genética , Sobrepeso/genética , Propiltiouracila/farmacologia , Receptores Acoplados a Proteínas G/genética , Percepção Gustatória/efeitos dos fármacos , Adolescente , Adulto , Negro ou Afro-Americano , Asiático , Biomarcadores , Índice de Massa Corporal , Estudos Transversais , Feminino , Estudos de Associação Genética , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Sobrepeso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto JovemRESUMO
For bumblebee colony survival, sugar responses are crucial as nectar is the main carbohydrate source and flower choice is likely determined by sugar composition. This study used a bioassay both with harnessed and with free-moving workers of the bumblebee Bombus terrestris to study the gustatory response to the 3 major plant sugars by both groups. In harnessed workers of B. terrestris, a concentration of 5.5% of fructose and glucose was required to induce the proboscis extension reflex in 50% of the workers, whereas for sucrose, a much higher concentration of 40% was needed. In contrast, free-moving workers given a choice between 30% glucose, 30% sucrose, 30% fructose, and water showed a strong preference for sucrose (66% of individuals) compared with 18% for glucose and 16% for fructose; water was never chosen. Familiarization with 30% fructose provoked a significant increase in preference toward fructose, indicating plasticity. In addition, by amputation of the tarsi, it was found that tarsi plays a role in the sugar response with especially the foreleg tarsi being involved in the response to fructose. Our results demonstrated that sugar response is different in free-moving versus harnessed bumblebee workers and that tarsi plays a role in sugar perception.