Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Clin Pharmacol Ther ; 82(1): 21-32, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17522597

RESUMO

The low productivity and escalating costs of drug development have been well documented over the past several years. Less than 10% of new compounds that enter clinical trials ultimately make it to the market, and many more fail in the preclinical stages of development. These challenges in the "critical path" of drug development are discussed in a 2004 publication by the US Food and Drug Administration. The document emphasizes new tools and various opportunities to improve drug development. One of the opportunities recommended is the application of "model-based drug development (MBDD)." This paper discusses what constitutes the key elements of MBDD and how these elements should fit together to inform drug development strategy and decision-making.


Assuntos
Ensaios Clínicos como Assunto/métodos , Relação Dose-Resposta a Droga , Aprovação de Drogas , Desenho de Fármacos , Modelos Biológicos , Farmacologia , Projetos de Pesquisa , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Aminas/farmacologia , Aminas/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Caproatos/farmacologia , Caproatos/uso terapêutico , Colesterol/sangue , Ensaios Clínicos como Assunto/legislação & jurisprudência , Ensaios Clínicos como Assunto/estatística & dados numéricos , Cognição/efeitos dos fármacos , Simulação por Computador , Ácidos Cicloexanocarboxílicos/farmacologia , Ácidos Cicloexanocarboxílicos/uso terapêutico , Gabapentina , Glicoproteínas/farmacologia , Glicoproteínas/uso terapêutico , Guias como Assunto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Metanálise como Assunto , Modelos Estatísticos , Agonistas Muscarínicos/farmacologia , Agonistas Muscarínicos/uso terapêutico , Neuralgia Pós-Herpética/tratamento farmacológico , Infiltração de Neutrófilos/efeitos dos fármacos , Oximas/farmacologia , Oximas/uso terapêutico , Farmacocinética , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/imunologia , Estados Unidos , United States Food and Drug Administration , Ácido gama-Aminobutírico/farmacologia , Ácido gama-Aminobutírico/uso terapêutico
2.
Naunyn Schmiedebergs Arch Pharmacol ; 335(3): 301-4, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3587372

RESUMO

The ability of a series of N6-modified N-alkyl-5'-uronamides to cause presynaptic inhibition of transmitter release was examined in isolated guinea-pig ileum stimulated at 0.2 Hz. These analogs inhibited the twitch responses to nerve stimulation, the majority being full agonists with their inhibitory effects being antagonised by theophylline. These analogs had no significant effects on responses of ileum to carbachol. N-ethyl 5'-uronamide substitution resulted in an up to four-fold reduction in activity of N6-substituted adenosine analogs, while stereoselectivity of the N6-substituted analogs continued to be present. 5'-Uronamide substitutions to N6-(3-pentyl)-adenosine resulted in a marked loss of activity when there were large alkyl groups at the amide or with amides of secondary amines. It was concluded that adenosine analogs interact with both the N6 and C-5' regions of the adenosine receptor in this tissue, with the interaction being less than additive.


Assuntos
Adenosina/análogos & derivados , Músculo Liso/efeitos dos fármacos , Receptores Purinérgicos/efeitos dos fármacos , Adenosina/farmacologia , Adenosina-5'-(N-etilcarboxamida) , Amidas/farmacologia , Animais , Estimulação Elétrica , Feminino , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Sinapses/efeitos dos fármacos
3.
Med Sci Sports Exerc ; 29(11): 1513-20, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9372490

RESUMO

The purpose of this study was to examine the accuracy and quality of a series of cycle ergometry tests used to estimate maximal aerobic capacity (VO2max). One-hundred nine males and 71 females participated in five tests: a maximal exercise test on the treadmill, three Air Force Cycle Ergometry Tests (AF1, AF2, AF3), and a Progressive cycle ergometry test (PROG). The VO2max value measured during the treadmill test was compared with the VO2max estimates from each ergometry test. The AF1, AF2, and AF3 results were used to determine reliability. The mean estimated VO2max for each, except the PROG, was significantly different (P < 0.05) from the measured VO2max. The AF1 and AF-avg tests underestimated VO2max by 8.0 and 6.5 mL.kg-1.min-1, respectively, values which were 17.3 and 14.9% lower than the measured VO2max. Correlation coefficients between estimated VO2max values and the measured VO2max ranged from 0.59 to 0.80 with SEE ranging from 1.8 to 2.2 mL.kg-1.min-1. The PROG had the greatest sensitivity (82.2%), while the AF2 had the greatest specificity (70.6%). Additionally, 23.4% of the VO2max estimates from the PROG were within +/- 5% of the measured VO2max compared with 9.9% for the average of the Air Force tests. The intraclass correlation coefficient for the three AF tests or the reliability for a single AF test was 0.26. In sum, the Air Force test provides an estimate of VO2max, and hence aerobic capacity, which is unreliable and underestimates the true VO2max by approximately 15%.


Assuntos
Exercício Físico/fisiologia , Consumo de Oxigênio , Aptidão Física , Adulto , Ergometria , Teste de Esforço/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
4.
Pharmacol Biochem Behav ; 64(3): 495-500, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10548261

RESUMO

Previous studies indicate that tyrosine may prove useful in promoting improved performance in situations in which performance is compromised by stress. To extend the generality of previous tyrosine findings, the present study examined the effects of tyrosine ingestion on performance during both a Multiple Task and a Simple Task battery. The multiple task battery was designed to measure working memory, arithmetic skills, and visual and auditory monitoring simultaneously, whereas the simple task battery measured only working memory and visual monitoring. Ten men and 10 women subjects underwent these batteries 1 h after ingesting 150 mg/kg of l-tyrosine or placebo. Administration of tyrosine significantly enhanced accuracy and decreased frequency of list retrieval on the working memory task during the multiple task battery compared with placebo. However, tyrosine induced no significant changes in performance on the arithmetic, visual, or auditory tasks during the Multiple Task, or modified any performance measures during the Simple Task battery. Blood levels of ACTH and cortisol were not, but heart rate and blood pressure were significantly increased during the performance tasks. The present results indicate that tyrosine may sustain working memory when competing requirements to perform other tasks simultaneously degrade performance, and that supplemental tyrosine may be appropriate for maintaining performance when mild to severe decrements are anticipated.


Assuntos
Memória de Curto Prazo/efeitos dos fármacos , Tirosina/farmacologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Atenção/efeitos dos fármacos , Percepção Auditiva/efeitos dos fármacos , Catecolaminas/sangue , Glândulas Endócrinas/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Estimulação Química , Tirosina/sangue , Percepção Visual/efeitos dos fármacos
6.
Arch Toxicol ; 62(2-3): 220-3, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3196157

RESUMO

A comparison of the chemical purity, toxicology and potency of HI-6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl]-pyridinium dichloride) obtained from various sources (Canada, Israel, Yugoslavia, The Netherlands, United Kingdom) was performed. There were no significant differences between HI-6 obtained from Israel, Yugoslavia, The Netherlands and Canada regarding their potency, when combined with atropine, as an antidote of organophosphate poisoning. HI-6 obtained from the United Kingdom was significantly more toxic and less potent than any of the other HI-6 samples. In addition, the results of this study showed that there was no significant difference between HI-6 prepared as a laboratory batch and HI-6 prepared commercially with regards to chemical purity, toxicology or potency.


Assuntos
Reativadores da Colinesterase/análise , Compostos de Piridínio/análise , Animais , Reativadores da Colinesterase/toxicidade , Contaminação de Medicamentos , Feminino , Dose Letal Mediana , Masculino , Camundongos , Oximas , Compostos de Piridínio/farmacologia , Compostos de Piridínio/toxicidade
7.
J Gen Microbiol ; 131(7): 1833-5, 1985 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-4045428

RESUMO

The in vitro toxicity of T-2 toxin towards mouse lymphoid cells prepared from spleen, thymus, peritoneal lavage and bone marrow cells was studied. Bone marrow cells were more resistant to damage by T-2 toxin than thymus, spleen and peritoneal cell preparations.


Assuntos
Medula Óssea/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Sesquiterpenos/farmacologia , Toxina T-2/farmacologia , Animais , Células da Medula Óssea , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Tecido Linfoide/citologia , Camundongos , Baço/citologia , Baço/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacos
8.
Anesthesiology ; 64(3): 359-63, 1986 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3954131

RESUMO

Contractile responses of isolated rabbit aortic strips to epinephrine and norepinephrine were potentiated in a dose-related manner by (+) ketamine but not by (-) ketamine (1.1 X 10(-5) M - 3.7 X 10(-4) M). Potentiation was blocked completely by pretreatment with the extraneuronal uptake inhibitor cortisol (83-138 microM) but was unaffected by the neuronal uptake inhibitor cocaine (29 microM). Responses of the rat anococcygeus muscle to these catecholamines were potentiated by both isomers, with (+) ketamine being more potent than its optical antipode. These effects were blocked completely in tissues from 6-hydroxydopamine sympathectomized animals. Results suggest that inhibition of extraneuronal uptake of catecholamines by racemic ketamine is due solely to an action of the (+) isomer, whereas both isomers appear capable of inhibiting neuronal uptake.


Assuntos
Catecolaminas/metabolismo , Ketamina/farmacologia , Neurônios/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Cocaína/farmacologia , Hidrocortisona/farmacologia , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Coelhos , Ratos , Estereoisomerismo
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa