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1.
Exp Clin Psychopharmacol ; 26(4): 329-334, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29878800

RESUMO

Addiction is characterized as a chronic debilitating disease. One devastating feature of addiction is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone, a primary stress hormone. PT150 is a novel glucocorticoid receptor antagonist that moderates the release of corticosterone. In the current experiment, it was hypothesized that subjects given repeated administration of PT150 would reduce sign tracking compared to subjects given placebo. Time spent (in seconds) near a cue that predicts reward (conditional stimulus) served as a measure of sign tracking, and PT150 or placebo was administered following sign tracking. An independent-samples t test revealed that subjects that received PT150 had reduced time spent near the conditioned stimulus compared to controls. Given the devastating effects of drug addiction, identification of a potential pharmacological intervention in the reduction of relapse would be of great value. Therefore, future research is needed to validate the use of PT150 in reducing behaviors associated with drug addiction. (PsycINFO Database Record


Assuntos
Comportamento Aditivo/tratamento farmacológico , Sinais (Psicologia) , Norpregnanos/farmacologia , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/fisiologia , Recompensa , Animais , Comportamento Aditivo/psicologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Coturnix , Masculino , Motivação/efeitos dos fármacos , Motivação/fisiologia , Norpregnanos/química , Norpregnanos/uso terapêutico , Ratos Sprague-Dawley
2.
Gynecol Endocrinol ; 31(5): 414-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25856298

RESUMO

The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3ß-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.


Assuntos
Endométrio/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Norpregnenos/farmacologia , Prolactina/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Western Blotting , Anticoncepcionais Femininos/farmacologia , Dexametasona/farmacologia , Endométrio/citologia , Endométrio/metabolismo , Ensaio de Imunoadsorção Enzimática , Estradiol/farmacologia , Estrenos/farmacologia , Estrogênios/farmacologia , Feminino , Furanos/farmacologia , Glucocorticoides/farmacologia , Antagonistas de Hormônios/farmacologia , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Acetato de Medroxiprogesterona/farmacologia , Mifepristona/farmacologia , Norpregnanos/farmacologia , Prolactina/genética , Prolactina/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Células Estromais/metabolismo
3.
Menopause ; 15(2): 386-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18000470

RESUMO

In an earlier study, we focused on the vasoactive effect of 3alpha-OH-tibolone on spontaneously constricted isolatedfemale rat gracilis muscle arterioles. Vasodilator effects (from 10 to 10 M) of 3alpha-OH-tibolone were similar to those of 17beta-estradiol. It was reported that 3beta-OH-tibolone like estradiol altered GABAB activation in neurons through a membrane estrogen receptor, whereas the 3alpha-OH metabolite did not. We therefore hypothesized that the 3beta-OH metabolite may also have a vasodilating effect in our isolated arteriole model. The results indicate that 3beta-OH-tibolone induces a vasodilator effect in small arterioles that is comparable with that of 3alpha-OH-tibolone at the same concentration. This is intriguing because the binding affinity of 3alpha-OH-tibolone to the estrogen receptor is almost twice that of 3beta-OH-tibolone. Other mechanisms may play a role.


Assuntos
Arteríolas/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Moduladores de Receptor Estrogênico/farmacologia , Norpregnanos/farmacologia , Norpregnenos/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Músculo Esquelético/irrigação sanguínea , Ratos , Ratos Wistar
4.
J Nat Prod ; 62(2): 318-20, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10075773

RESUMO

Two new norpregnane glycosides, 19-norpregna-1,3,5(10), 20-tetraen-3-O-alpha-fucopyranoside (3) and 19-norpregna-1,3,5(10), 20-tetraen-3-O-beta-arabinopyranoside (4), were isolated from the soft coral Scleronephthya pallida, along with two known steroids, pregna-1,20-dien-3-one (1) and 19-norpregna-1,3,5(10), 20-tetraen-3-ol (2). 19-Norpregna-1,3,5(10), 20-tetraen-3-O-alpha-fucopyranoside (3) exhibits moderate antimalarial and cytotoxic activities. The chemical structures of 1-4 were elucidated from spectroscopic data.


Assuntos
Antimaláricos/isolamento & purificação , Cnidários/química , Glicosídeos/isolamento & purificação , Norpregnanos/isolamento & purificação , Animais , Antimaláricos/química , Antimaláricos/farmacologia , Sequência de Carboidratos , Glicosídeos/química , Glicosídeos/farmacologia , Norpregnanos/química , Norpregnanos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Análise Espectral
5.
J Steroid Biochem Mol Biol ; 55(1): 77-84, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7577723

RESUMO

Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions. The binding specificity respected a decreasing order as follows: estradiol (E2: 100%) > 4-hydroxy-tamoxifen (4OHTAM: 52.7%) > estriol (E3: 5.7%) > estrone (E1: 2.1%) > TAM (0.2%). The induction of alkaline phosphatase activity (APase) used as an estrogen-specific response, confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT): norethindrone (NOR), norethynodrel and levonorgestrel, at concentrations ranging from 10(-8) to 10(-6) M. The effect of NOR was partially blocked by the antiestrogen 4OHTAM, which was also partially agonistic in this model, but neither by the antiprogestin mifepristone (RU486) nor by the aromatase inhibitor aminoglutethimide. A simulatory effect was also detected at 10(-7) or 10(-6) M with ethindrone, the testosterone- (T) derived progestin homologous to NOR, and with both androgenic parent-compounds, i.e. T and 19NT themselves. In contrast, progesterone (P) derivatives like medroxyprogesterone acetate (MPA) and chlormadinone acetate (CMA) remained totally inactive, as well as 19-nor-progesterone (19NP) itself or its progestagenic derivatives: ORG 2058 and nomegestrol acetate (NOM). Structure-activity relationships deduced from these studies suggest that it is not the absence of the 19-methyl group which can account for the estrogenic potential of the so-called "19-norprogestins", but rather their steroid structure derived from T in a broad sense (including the 19NT derivatives), as opposed to the non-estrogenic therapeutic progestins derived from P like MPA or CMA, or from 19NP like NOM.


Assuntos
Endométrio/efeitos dos fármacos , Estrogênios/farmacologia , Norpregnanos/farmacologia , Progesterona/análogos & derivados , Progestinas/farmacologia , Testosterona/análogos & derivados , Adenocarcinoma , Fosfatase Alcalina/biossíntese , Aminoglutetimida/farmacologia , Inibidores da Aromatase , Ligação Competitiva , Citosol/metabolismo , Neoplasias do Endométrio , Endométrio/citologia , Endométrio/metabolismo , Indução Enzimática , Inibidores Enzimáticos/farmacologia , Congêneres do Estradiol/metabolismo , Estrogênios/metabolismo , Etinilestradiol/análogos & derivados , Etinilestradiol/metabolismo , Feminino , Humanos , Nandrolona/análogos & derivados , Nandrolona/farmacologia , Norprogesteronas/farmacologia , Pregnanos/farmacologia , Receptores Estrogênicos/metabolismo , Tamoxifeno/farmacologia , Células Tumorais Cultivadas
7.
Invest. med. int ; 14(3): 197-201, nov. 1987. tab
Artigo em Espanhol | LILACS | ID: lil-48193

RESUMO

Se estudió el efecto anticonceptivo, los efectos secundarios y las modificaciones en los sangrados menstruales, el peso corporal, la presión arterial y constantes de laboratorio, en dos grupos de mujeres: el primero utilizando la mezcla anticonceptiva de 150 mcg de desogestrel y 30 mcg de etinil estradiol y el segundo la de 150 mcg de levo-norgestrel y 30 mcg de etinil estradiol. Se estudiaron en total 252 mujeres, durante 4.332 ciclos, con un tiempo máximo de consumo de 34 ciclos. Los resultados mostraron un muy favorable efecto del desogestrel/etinil estradiol sobre el peso corporal, que no aumentó sino aun disminuyó con esta mezcla, la cual además produjo menores alteraciones del sangrado menstrual, mínimos e insignificantes efectos secundarios, gran tolerancia y un alto índice de continuidad de 89%


Assuntos
Adulto , Feminino , Norpregnanos/farmacologia , Norpregnanos/efeitos adversos
8.
Fortschr Med ; 95(29): 1827-32, 1977 Aug 04.
Artigo em Alemão | MEDLINE | ID: mdl-885464

RESUMO

The contraceptive effect of continuous treatment with low dose progestogens (minipill) has been attributed mainly to alterations of the cervical mucus and the endometrium. This study was undertaken to investigate the effect of low dose progestogens on hypothalamic-pituitary-ovarian function. Plasma concentrations of follicle stimulating hormone (FSH), luteininzing hormone (LH), estradiol-17 beta (E-2) and Progesterone were measured daily during apparently ovulatory menstrual cycles and during treatment cycles with different low dose progestogens. From the results obtained it was concluded that the minipill has a clear-cut effect on the LH/FSH peak at midcycle and on corpus luteum function. A cyclic secretion of E-2 is maintained in the majority of cases. In a few treatment cycles however, follicular maturation was suppressed as indicated by low E-2 concentrations. It was concluded that the minipill exerts a profound effect at the central and ovarian level which contributes to its satisfactory contraceptive efficacy.


Assuntos
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Norpregnanos/farmacologia , Ovário/efeitos dos fármacos , Adulto , Feminino , Humanos , Linestrenol/farmacologia , Noretindrona/farmacologia , Norgestrel/farmacologia
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