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1.
Magn Reson Chem ; 49(7): 425-36, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21590729

RESUMO

Indirect and unsymmetrical indirect covariance NMR provide powerful tools to compute and visualize correlation information by transforming component spectra into combined spectral data matrices. Sensitive component spectra such as TOCSY, HSQC and NOESY can be quickly converted into experimentally insensitive or time-consuming correlation spectra such as HSQC-NOESY. The comparison of illustrative series of spectra from four steroids, dexamethasone, testosterone, allylestrenol and tibolone, renders the effects of resonance overlap on the ease of interpretation visible. The compounds are selected such that signal overlap increases systematically in the proton and carbon domain. Spectra are defined as light, moderate and heavy signal overlap, based on signal density. The investigation suggests that moderate spectral congestion in either proton or carbon domain leads to a number of artifacts that does not hamper signal assignment but lowers the level of confidence on de novo structure elucidation. Since the number of correlations usually increases through covariance processing, component spectra with severe spectral congestion in both dimensions are not suitable for covariance processing and the resulting spectra do not support structure confirmation or structure elucidation. The calculated spectra are compared with the corresponding experimental spectra with respect to their application in structure elucidation laboratory environments.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Alilestrenol , Dexametasona , Estrutura Molecular , Norpregnenos , Processamento de Sinais Assistido por Computador , Esteroides/química , Testosterona
2.
Artigo em Inglês | MEDLINE | ID: mdl-18639502

RESUMO

A sensitive, specific and rapid liquid chromatographic/tandem mass spectrometric (LC/MS/MS) assay for the determination of allylestrenol in human plasma was established. Plasma samples were extracted by tert-butyl ether and separated by LC/MS/MS using a Phenomenex Curosil-PFP column (250 mm x 4.6 mm ID, dp 5 microm) with a mobile phase of methanol-water (95:5, v/v). The analytes were monitored with atmospheric pressure chemical ionization (APCI) by selected reaction monitoring (SRM) mode. The linear calibration curves covered a concentration range of 0.04-20.0 ng/mL with lower limit of quantification (LLOQ) at 0.04 ng/mL. The mean extraction recovery of allylestrenol was greater than 81.8%. The intra- and inter-day precisions were less than 1.3% and 3.1% respectively, determined from quality control (QC) samples of three representative concentrations. The method has been successfully applied to determining the plasma concentration of allylestrenol and a clinical pharmacokinetics study in healthy Chinese female volunteers.


Assuntos
Alilestrenol/farmacocinética , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Adulto , Grupo com Ancestrais do Continente Asiático , China , Estabilidade de Medicamentos , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Prostate ; 67(8): 799-807, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17373727

RESUMO

BACKGROUND: Molecular basis for secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) is not fully elucidated. MATERIALS AND METHODS: Effects of steroidal and non-steroidal antiandrogens on transcriptional activities of wild-type and mutant (W741C, T877A, and W741C+T877A) ARs were measured. Crystal structure analysis and docking studies were performed using Molecular Operating Environment (MOE) package. RESULTS: DHT-induced transcriptional activity of the T877A mutant and the W741C mutant was suppressed by bicalutamide and hydroxyflutamide, respectively. Nilutamide suppressed the W741C mutant and the double mutant. Cyproterone acetate modestly inhibited the W741C mutant and the double mutant. The structural studies suggested that nilutamide and cyproterone acetate retain their antiandrogenic properties against both the W741C mutant and the double mutant due to fact that mutation W741C does not permit formation of key hydrophobic interaction between ligand and AR ligand binding domain, which is necessary for their conversion into agonists. CONCLUSIONS: Switching antiandrogens may be reasonable in prostate cancer with mutant ARs.


Assuntos
Antagonistas de Androgênios/farmacologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/genética , Alilestrenol/farmacologia , Antagonistas de Androgênios/química , Antagonistas de Receptores de Andrógenos , Androgênios , Anilidas/química , Anilidas/farmacologia , Acetato de Ciproterona/química , Acetato de Ciproterona/farmacologia , Flutamida/análogos & derivados , Flutamida/química , Flutamida/farmacologia , Humanos , Imidazolidinas/química , Imidazolidinas/farmacologia , Masculino , Modelos Moleculares , Mutagênese Sítio-Dirigida , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/metabolismo , Nitrilos/química , Nitrilos/farmacologia , Plasmídeos/genética , Antígeno Prostático Específico/biossíntese , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Neoplásico/química , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testosterona/análogos & derivados , Testosterona/farmacologia , Compostos de Tosil/química , Compostos de Tosil/farmacologia , Transcrição Genética/efeitos dos fármacos , Transfecção
4.
Hinyokika Kiyo ; 52(7): 527-30, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16910584

RESUMO

Decrease in serum prostate specific antigen (PSA) concentration is inevitably associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and might mask the presence of prostate cancer or delay its diagnosis. To determine the appropriate timepoint for determination of correct PSA value, we sequentially measured serum PSA and testosterone levels after discontinuation of antiandrogen therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old) with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum testosterone and PSA concentrations were determined before and just after treatment, as well as every month after treatment up to 3 months. After treatment with allylestrenol for 4 months, mean serum testosterone and PSA levels were significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81 +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level recovered to the pretreatment level within 2 months and mean serum testosterone concentration within one month after discontinuation of administration. In conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month washout is adequate for determination of correct PSA value (*: M +/- SD).


Assuntos
Alilestrenol/uso terapêutico , Congêneres da Progesterona/uso terapêutico , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/tratamento farmacológico , Testosterona/sangue , Antagonistas de Androgênios/uso terapêutico , Humanos , Masculino , Hiperplasia Prostática/sangue , Fatores de Tempo
5.
Hinyokika Kiyo ; 48(5): 269-73, 2002 May.
Artigo em Japonês | MEDLINE | ID: mdl-12094708

RESUMO

One hundred and twenty-nine patients with benign prostatic hypertrophy (BPH) were registered and treated with allylestrenol. Allylestrenol was administered at a dose of 50 mg/day given twice a day for 16 weeks. Out of 129 patients with a mean age of 67.8 years old, 92 cases completed the study and 48 cases with moderate symptoms were objectively evaluated with "Criteria for Treatment Efficacy in BPH" proposed by The Japanese Urological Association in 1997. Prostate volume was significantly decreased from 32.7 +/- 11.9 to 27.4 +/- 11.2 ml (mean +/- SD), and maximum flow rate was significantly increased from 8.4 +/- 3.4 to 10.8 +/- 5.0 ml/sec. Residual urine volume was significantly decreased from 62.4 +/- 57.4 to 37.0 +/- 38.7 ml. IPSS was significantly decreased from 15.3 +/- 4.9 to 9.9 +/- 4.0, and QOL index was significantly decreased from 4.4 +/- 0.8 to 2.7 +/- 1.2. The efficacy of allylestrenol was shown by its effects on prostate volume (anatomy), maximum urinary flow rate (function), and symptom scores (symptom) at the end of 16 weeks of treatment. The rates of improvement for symptoms, QOL, function, and anatomy are 68.7% (N = 48), 79.2% (N = 48), 50.0% (N = 48), and 61.0% (N = 41), respectively. Overall efficacy (Good and Fair) was 70.9% (N = 48). During this study, 5 patients (3.9%) complained of loss of libido and 2 patients dropped out. In conclusion, allylestrenol was demonstrated to be a quite effective and safe medical treatment for patients with symptomatic BPH based on the criteria for treatment efficacy in BPH.


Assuntos
Alilestrenol/uso terapêutico , Congêneres da Progesterona/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Hiperplasia Prostática/fisiopatologia , Qualidade de Vida , Sistema de Registros
6.
Acta Physiol Hung ; 88(2): 131-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11999805

RESUMO

Hormonal imprinting takes place perinatally, at the first encounter between the target hormone and its developing receptor. However, there is a secondary critical period of imprinting at puberty. In these periods molecules similar to the hormones (members of the same hormone family, antagonists, certain environmental pollutants, etc.) can cause faulty imprinting with lifelong consequences. In the present experiments 5+2 days of tamoxifen treatment (120 microg/day) at adolescent age dramatically (from approx. 40% to 10%) reduced the sexual activity (Meyerson index and lordosis quotient) of female rats, soon after the finishment of the treatment and between four to six weeks after treatment. Similar results were observed in animals neonatally treated with allylestrenol and tamoxifen treated at puberty. Thymic glucocorticoid receptor and uterine estrogen receptor binding capacity were not influenced.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/psicologia , Antagonistas de Estrogênios/farmacologia , Receptores Estrogênicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Tamoxifeno/farmacologia , Alilestrenol/farmacologia , Animais , Feminino , Congêneres da Progesterona/farmacologia , Ratos , Ratos Wistar , Receptores Estrogênicos/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos
7.
Hinyokika Kiyo ; 46(9): 605-7, 2000 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-11107528

RESUMO

We compared the prostate specific antigen (PSA) levels in benign prostatic hyperplasia (BPH) patients with antiandrogen chlormadinone acetate (CMA) or allylestrenol (AE) before and during the treatment. We also investigated the serial change of PSA levels before, during and after discontinuation of antiandrogen therapy. Fifty-one BPH patients with normal PSA levels were treated with CMA or AE for 16 weeks. The mean serum PSA level significantly decreased after the treatment from 1.9 +/- 1.0 ng/ml to 1.1 +/- 0.7 ng/ml (M +/- SD). We discontinued medication with informed consent and the patients were carefully monitored for another 16 weeks. Nineteen patients were followed for 32 weeks. The mean serum PSA level decreased significantly from 2.0 +/- 1.0 ng/ml to 1.1 +/- 0.5 ng/ml (M +/- SD) and recovered approximately to the pretreatment level (1.7 +/- 1.1 ng/ml) at the end of this study. We found only one patient whose PSA was slightly elevated to a subnormal range (4.3 ng/ml) after discontinuation of therapy. The other BPH patients with normal PSA levels showed no excessive increase in PSA levels beyond the normal limit after discontinuation of antiandrogen therapy compared with the pretreatment baseline. In conclusion, BPH patients with a marked increase in PSA after discontinuation of antiandrogen therapy should be checked for prostate cancer.


Assuntos
Alilestrenol/administração & dosagem , Antagonistas de Androgênios/administração & dosagem , Acetato de Clormadinona/administração & dosagem , Congêneres da Progesterona/administração & dosagem , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/sangue
9.
Life Sci ; 64(9): PL105-10, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10075115

RESUMO

Neonatal treatment with allylestrenol or diethylstilbestrol (DES) reduced the bone mineral content (BMC/bw) of the adult (four months old) female rats, without influencing bone mineral density (BMD/bw). In males these neonatal treatments elevated BMC and BMD alike. Ovariectomy alone decreased BMC and BMD alike; however the neonatal hormone treatments did not influence this reduced value. Ovariectomy of two months old animals increased body weight without the influence of neonatal hormone treatments. In adult males, the body weight was reduced significantly by neonatal DES and non-significantly by neonatal allylestrenol treatment. The experiments call attention to the possible human bone-effects of allylestrenol, which was used in the last decades as medication protecting endangered pregnancies.


Assuntos
Alilestrenol/farmacologia , Densidade Óssea/efeitos dos fármacos , Dietilestilbestrol/farmacologia , Estrogênios não Esteroides/farmacologia , Congêneres da Progesterona/farmacologia , Absorciometria de Fóton , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/fisiologia , Feminino , Impressão Genômica , Masculino , Ovariectomia , Ratos , Ratos Wistar
10.
Mutat Res ; 419(1-3): 33-41, 1998 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-9804880

RESUMO

Progesterone (PG) and three structurally similar synthetic progestins-norethisterone (NE), allylestrenol (AE), and dydrogesterone (DG)-have been compared for their ability to induce the formation of micronuclei and of enzyme-altered foci in the liver of female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg kg-1 3 days before partial hepatectomy and sacrificed for cell sampling 2 days later, the frequency of micronucleated hepatocytes was 3.5-fold higher than in controls with PG, 2.8-fold with DG, 2.2-fold with NE and 2.1-fold with AE, but the increase was statistically significant only for PG. In the liver foci assay, performed to evaluate the tumor initiating activity of p. o. dosing with 100 mg kg-1 once a week for 6 successive weeks, the values of the number and area of gamma-glutamyltranspeptidase-positive foci were, as compared to controls, 15.9- and 100-fold higher with NE, and 13.9- and 52-fold higher with AE, but only the increase of area produced by NE was statistically significant; PG and DG did not display in this test any activities. Considered together with previous findings, these results suggest that NE might be biotransformed in the liver into reactive species and thus behave as a weak genotoxic agent.


Assuntos
Carcinógenos/toxicidade , Fígado/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico , Mutagênicos/toxicidade , Congêneres da Progesterona/toxicidade , Progesterona/toxicidade , Alilestrenol/química , Alilestrenol/toxicidade , Animais , Biotransformação , Acetato de Ciproterona/química , Acetato de Ciproterona/toxicidade , Didrogesterona/química , Feminino , Fígado/enzimologia , Fígado/patologia , Testes para Micronúcleos , Noretindrona/química , Noretindrona/toxicidade , Ratos , Ratos Sprague-Dawley , gama-Glutamiltransferase
11.
Int J Urol ; 5(5): 466-70, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9781436

RESUMO

BACKGROUND: A multicenter, clinical trial investigated the effects of an interruption of antiandrogen therapy on subjective and objective clinical parameters in patients with benign prostatic hypertrophy (BPH). METHODS: Patients were given antiandrogen therapy with allylestrenol (50 mg/day) for 16 weeks. The medication was then withheld and the patients were carefully monitored for an additional 16 weeks. There were 34 BPH patients ranging in age from 55 to 82 years (mean, 66.1 years). The efficacy of allylestrenol was evaluated by its effects on prostate volume, maximum urinary flow rate (MFR), and symptom scores at the end of 16 weeks of treatment and then again at 32 weeks (16 weeks after cessation of therapy). RESULTS: Allylestrenol was effective in the treatment of BPH, and was still effective 16 weeks after the cessation of medication. The prostate volume did not change after treatment cessation nor did the total symptom score, but the MFR reversed to the pretreatment level. Serum testosterone (1.95 ng/mL), dihydrotestosterone, and gonadotropin levels decreased on therapy, but were completely reversed by the end of this study. A prostate needle biopsy revealed that after 16 weeks without therapy, some glands showed regressive glandular changes, while some glands showed slight hyperplastic changes of the secretory epithelium. Eight per cent of patients complained of loss of libido during this study. CONCLUSIONS: Allylestrenol is an effective and safe medical treatment for patients with symptomatic BPH. Hormonal and histopathologic findings suggest that the prostate gland may regrow after discontinuation of medication.


Assuntos
Alilestrenol/uso terapêutico , Congêneres da Progesterona/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Seguimentos , Hormônios Esteroides Gonadais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Estudos Retrospectivos , Segurança , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos
12.
Gen Pharmacol ; 29(5): 779-81, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9347325

RESUMO

1. Combined neonatal imprinting with allylestrenol, vitamins A and D3 and benzpyrene significantly increased thymic glucocorticoid receptor capacity in male and female animals and decreased receptors affinity in adult females only. 2. Uterine estrogen receptor affinity or density was not influenced. 3. Considering that perinatal treatment with allylestrenol or vitamin D3 decreased glucocorticoid receptor capacity, the dominance of the positive effect of retinol should be surmised. 4. The experiments call attention to the interrelation of different materials acting simultaneously in the perinatal period.


Assuntos
Alilestrenol/farmacologia , Animais Recém-Nascidos/fisiologia , Benzo(a)pireno/farmacologia , Colecalciferol/farmacologia , Receptores Estrogênicos/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Timo/metabolismo , Útero/metabolismo , Vitamina A/farmacologia , Animais , Anti-Inflamatórios/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Dexametasona/metabolismo , Feminino , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Timo/efeitos dos fármacos , Útero/efeitos dos fármacos
13.
Jpn J Pharmacol ; 74(3): 243-52, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9268084

RESUMO

ONO-9302 [epristeride; (-)-17beta-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxy lic acid] is a novel inhibitor of steroid 5alpha-reductase. We studied in vitro and in vivo effects of ONO-9302 on the rat prostatic tissue in comparison with those of the anti-androgen allylestrenol. ONO-9302 inhibited the rat prostatic enzyme with an IC50 value of 11 nM, whereas allylestrenol was about 80,000-fold less potent. The growth of ventral prostate, which was induced by the subcutaneous injection of testosterone propionate in the castrated rats, was significantly reduced by ONO-9302 at oral doses of 1-100 mg/kg/day. Allylestrenol showed a significant effect only at a dose of 100 mg/kg/day. In mature male rats, ONO-9302 significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day and decreased prostatic 5alpha-dihydrotestosterone (DHT) content associated with a rise in testosterone (T) content at doses of 0.1-100 mg/kg/day. Plasma hormone levels (i.e., T, DHT, luteinizing hormone (LH) and follicle stimulating hormone (FSH)) were not altered significantly. Allylestrenol significantly reduced the ventral prostate weight at doses of 10-100 mg/kg/day. However, unlike ONO-9302, allylestrenol reduced both the prostatic DHT and T contents and also lowered plasma T, DHT, LH and FSH levels at a dose of 30 mg/kg/day. These results suggest that ONO-9302 reduces the prostatic growth by inhibiting the conversion of T to DHT in the prostate without lowering blood T level unlike anti-androgen drugs.


Assuntos
Inibidores de 5-alfa Redutase , Alilestrenol/farmacologia , Antagonistas de Receptores de Andrógenos , Androstadienos/farmacologia , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Congêneres da Progesterona/farmacologia , Próstata/efeitos dos fármacos , Testosterona/metabolismo , Animais , Inibidores Enzimáticos/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Ratos , Ratos Sprague-Dawley , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos , Testosterona/farmacologia
14.
Br J Urol ; 80(1): 78-83, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9240185

RESUMO

OBJECTIVE: To determine whether transrectal ultrasonography (TRUS) can predict the clinical response of patients with benign prostatic hypertrophy (BPH) to alpha 1-blocker and anti-androgen therapy. PATIENTS AND METHODS: From April 1994 to July 1995, 128 patients with BPH were randomized to treatment for 6 months with either tamsulosin (a long-acting selective alpha 1-blocker) or allylestrenol (an anti-androgen), with 64 patients receiving tamsulosin (0.2 mg/day) and 64 receiving allylestrenol (50 mg/day). The results of TRUS, uroflowmetry and the American Urologic Association (AUA) symptom score were compared before and after treatment. TRUS was used to calculate the transition zone (TZ) volume, transition zone ratio (TZ ratio = TZ volume/total prostate volume), total prostate volume and prostate-specific antigen density (PSAD). RESULTS: Both groups showed a statistically significant improvement in the AUA symptom score, quality-of-life (QOL) score and peak urinary flow rate (Qmax) at 6 months (P < 0.001). In the tamsulosin group, there was a significant negative correlation between the pretreatment PSAD and the percentage change in Qmax (r = -0.640, P < 0.001), while there was a positive correlation between PSAD and the percentage change in the AUA symptom score (r = 0.589, P < 0.001). On the other hand, the allylestrenol group showed a significant positive correlation between PSAD and the percentage change in Qmax (r = 0.397, P < 0.01) and a negative correlation between PSAD and the AUA symptom score (r = -0.313, P < 0.01). CONCLUSION: Patients with a high pretreatment PSAD responded well to anti-androgen therapy, while those with a low PSAD responded better to alpha 1-blocker therapy.


Assuntos
Antagonistas Adrenérgicos alfa/uso terapêutico , Alilestrenol/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Tansulosina , Resultado do Tratamento , Transtornos Urinários/fisiopatologia , Urodinâmica
15.
Jpn J Pharmacol ; 74(2): 187-94, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9243327

RESUMO

FK143 (4-[3-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl] - butyric acid) is a new non-steroidal inhibitor of steroid 5 alpha-reductase (5 alpha-reductase). The effects of FK143 on prostate size and histopathology of mature male beagle dogs were investigated and compared with those of finasteride (a steroidal 5 alpha-reductase inhibitor), and allylestrenol and chlormadinone acetate (CMA) (androgen receptor antagonists). FK143 was orally administered to the dogs daily for 12 weeks. At doses of 10 and 32 mg/kg, FK143 significantly reduced prostate volume to about 60% of the initial value, and dogs treated with FK143 showed a dose-dependent glandular epithelial atrophy in the prostate. FK143 showed no abnormal changes in organ weights and histopathology of the adrenal, testis, pituitary and liver. The degree of prostate reduction in the dogs treated with FK143 (10 and 32 mg/kg) was almost the same as that by finasteride (1.0 mg/kg) and smaller than that by allylestrenol (10 mg/kg) or CMA (10 mg/kg). However, allylestrenol increased liver weights, and CMA increased liver and reduced adrenal weights. These results demonstrate that FK143 can decrease the volume of the dog prostate without any influence on other organs, and they suggest that FK143 is a good candidate for the treatment for benign prostatic hyperplasia.


Assuntos
Inibidores de 5-alfa Redutase , Indóis/farmacologia , Fenilbutiratos/farmacologia , Próstata/efeitos dos fármacos , Alilestrenol/farmacologia , Antagonistas de Receptores de Andrógenos , Animais , Acetato de Clormadinona/farmacologia , Cães , Finasterida/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Congêneres da Progesterona/farmacologia , Próstata/citologia , Próstata/diagnóstico por imagem , Ligação Proteica/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Ultrassonografia
16.
Gen Pharmacol ; 27(8): 1387-9, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9304412

RESUMO

1. Neonatal treatment with allylestrenol caused an increase in the number of glucocorticoid receptors in the thymus in the adult. 2. Benzpyrene treatment of adult animals persistently reduced the glucocorticoid receptor number in rats that were not submitted to neonatal treatment. This effect was not observed in adult animals following neonatal treatment with allylestrenol. 3. The experiment calls attention to the permanent effect of steroid imprinting and to the developmental stage dependence of the direction of imprinting. 4. The effect of neonatal steroid treatment on a later steroid influence is also demonstrated.


Assuntos
Alilestrenol/farmacologia , Benzo(a)pireno/farmacologia , Congêneres da Progesterona/farmacologia , Receptores de Glucocorticoides/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Citosol/química , Citosol/metabolismo , Dexametasona/metabolismo , Masculino , Ligação Proteica/efeitos dos fármacos , Ratos , Timo/química
17.
Acta Physiol Hung ; 84(2): 131-7, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9046359

RESUMO

In neonatally allylestrenol treated animals in adult age a single benzpyrene treatment significantly decreases the female and significantly increases the male rat's sexual activity. Three month old females display the negative sexual behavioral effect of neonatal allylestrenol treatment less than the six month old ones. The benzpyrene treatment in adult age decreases the sexual activity of male rats. The experiments call the attention to the modifying effect of perinatal steroid treatments to similar exposure in adult age.


Assuntos
Alilestrenol/farmacologia , Benzopirenos/toxicidade , Comportamento Sexual Animal/efeitos dos fármacos , Envelhecimento , Animais , Animais Recém-Nascidos , Ejaculação/efeitos dos fármacos , Feminino , Masculino , Postura , Ratos , Ratos Wistar , Caracteres Sexuais
18.
Horm Metab Res ; 28(1): 16-9, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8820988

RESUMO

Uterus estrogen receptor affinity increases in adult rats if treated with contraceptive, without receptor density change. Uterus estrogen receptor density decreases in adulthood following allylestrenol (Gestanon) treatment perinatally with receptor affinity unchanging. In perinatally allylestrenol treated rats contraceptive treatment resulted in the decrease of receptor affinity and increase of density, related to the only perinatally allylestrenol treated animals. The results draw attention to the fact that contraceptives may influence the estrogen receptor state of the uterus and the pregnancy maintaining treatment (by allylestrenol) may influence the state of uterine estrogen receptors for life via the later effect of contraceptives commonly dosed.


Assuntos
Anticoncepcionais Orais Hormonais/farmacologia , Receptores Estrogênicos/efeitos dos fármacos , Útero/metabolismo , Alilestrenol/farmacologia , Animais , Animais Recém-Nascidos , Congêneres do Estradiol/farmacologia , Etinilestradiol/farmacologia , Feminino , Cinética , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Norgestrel/farmacologia , Congêneres da Progesterona/farmacologia , Ratos , Útero/efeitos dos fármacos
19.
Nihon Hinyokika Gakkai Zasshi ; 86(5): 1044-50, 1995 May.
Artigo em Japonês | MEDLINE | ID: mdl-7541089

RESUMO

Anti-androgenergic agents are usually used for patients with benign prostatic hypertrophy (BPH). However steroidal anti-androgenergic agents tend to suppress the sexual function. This side effect is very significant in middle-aged men. Therefore we studied the preventive effect of indeloxazine hydrochloride (INDX), which induces an increase of the dopamine level in the brain, on the sexual dysfunction induced by an anti-androgenergic agent (allylestrenol: ALE). Thirty-six patients with BPH were classified into two groups, one used ALE only, and the other ALE with INDX. For the subjective evaluation of the sexual function, a self assessment questionnaire method was employed before and after administration. We especially studied 3 questions, "morning erection", "erectile capacity" and "frequency of sex". For the objective evaluation of the sexual function, nocturnal penile tumescence (NPT) was measured using an erectometer. NPT occurs in healthy males as a physiological phenomenon and it shows the erectile capacity objectively. The levels of LH, total testosterone and free testosterone were also determined. In the ALE only group, sexual dysfunction was found subjectively and objectively, but in the ALE with INDX group, it was not found. Levels of LH, total testosterone and free testosterone were decreased in the both groups. There was no significant difference between the two groups. We hypothesized that the sexual dysfunction due to ALE is related with not only to the decrease of androgen, but also to suppression of the central nervous system; for example, the suppression of the area of the brain mediating sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Alilestrenol/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Morfolinas/uso terapêutico , Disfunções Sexuais Fisiológicas/prevenção & controle , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamente
20.
Gen Pharmacol ; 26(2): 365-7, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7590089

RESUMO

1. Female rats were treated with allylestrenol on the 15th, 17th and 19th days of their pregnancy. 2. Serum testosterone and progesterone level of their three months old offspring were higher than control in males and females, respectively. 3. Serum progesterone levels of females, treated both prenatally and in adulthood, does not differ from control values. Serum testosterone level of males, treated prenatally and in adulthood, is lower than control. 4. One single allylestrenol treatment in adulthood does not make changes in testosterone concentration in males, but progesterone level is elevated in females. 5. Our experiments draw attention to the dangers of prenatal allylestrenol treatments (administered in case of endangered pregnancies) which may have long lasting effects on sexual steroid hormone levels.


Assuntos
Alilestrenol/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Progesterona/sangue , Testosterona/sangue , Envelhecimento/sangue , Animais , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar
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