Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Psychoneuroendocrinology ; 36(10): 1460-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21531081

RESUMO

INTRODUCTION: The hypothalamus-pituitary-adrenal (HPA)-axis is often found to be dysregulated in bipolar disorder (BD) while stress and changes in day-night rhythms can trigger a new mood episode. Genetic variants of the glucocorticoid receptor (GR)- and mineralocorticoid receptor (MR)-gene influence both the reactivity of the stress-response and associate with changes in mood. In this study we tested the hypothesis that these polymorphisms associate with different clinical characteristics of BD. METHODS: We studied 326 outpatients with BD and performed GR genotyping of the TthIIII, ER22/23EK, N363S, BclI, and 9ß polymorphisms, as well as MR genotyping of the 2G/C and I180V variants. All patients were interviewed for clinical characteristics. RESULTS: Seasonal patterns of hypomania are related to the BclI haplotype and the TthIIII+9ß haplotype of the GR gene (respectively, crude p=.007 and crude p=.005). Carriers of the ER22/23EK polymorphism had an almost 8 years earlier onset of their first (hypo)manic episode than non-carriers (crude p=.004, after adjustment p=.016). No evidence for a role of the MR in modifying clinical manifestations was found. CONCLUSION: Polymorphisms of the GR-gene are factors which influence some clinical manifestations of BD, with respect to seasonal pattern of (hypo)mania and age of onset.


Assuntos
Transtorno Bipolar/genética , Polimorfismo Genético , Receptores de Glucocorticoides/genética , Receptores de Mineralocorticoides/genética , Adulto , Idade de Início , Transtorno Bipolar/epidemiologia , Estudos Transversais , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fenótipo , Estações do Ano
2.
J Clin Psychopharmacol ; 20(5): 538-43, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11001238

RESUMO

The authors conducted an open-label study of the efficacy and tolerability of venlafaxine and of lithium augmentation in outpatients with depression who were not responding to venlafaxine. Outpatients aged 18 to 70 years were eligible if they had a minimum baseline score of 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D). Patients were started on venlafaxine 37.5 mg twice daily for 1 week. For weeks 2 through 4, the dose of venlafaxine was increased to 75 mg twice daily, and for weeks 5 through 7, the dose was further increased to 75 mg three times daily. At the end of the 7-week treatment period, patients with a <50% decrease in their HAM-D scores from baseline were given lithium carbonate 600 mg once daily. The dose of lithium carbonate was adjusted to maintain plasma levels in the range of 0.6 to 1.0 mmol/mL. Efficacy was assessed with the 17-item HAM-D, Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions Scale. Data were analyzed on an intent-to-treat basis. At the end of the 7-week treatment period, 35% of patients showed a > or = 50% decrease in their HAM-D scores from baseline. Lithium augmentation was initiated in 23 patients. The results showed that the addition of lithium was well-tolerated and led to a further decrease in the HAM-D scores, with eight patients responding and two of them presenting a remission. The addition of lithium to venlafaxine was found to be a well-tolerated strategy in treatment-resistant patients.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Antimaníacos/uso terapêutico , Cicloexanóis/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Lítio/uso terapêutico , Adulto , Idoso , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacocinética , Antimaníacos/efeitos adversos , Cicloexanóis/efeitos adversos , Cicloexanóis/farmacocinética , Transtorno Depressivo/psicologia , Quimioterapia Combinada , Feminino , Humanos , Lítio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Cloridrato de Venlafaxina
4.
Drug Metabol Drug Interact ; 9(2): 139-48, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1800019

RESUMO

beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (48 h) exposure of rats to N2O. However, a significant decrease of beta-endorphin was found in the whole brain, brain stem and subcortex during the withdrawal from chronic exposure to N2O. It has been suggested that decrease of beta-endorphin levels during N2O withdrawal could be ascribed to unspecific stress accompanying drug withdrawal. Decrease of central beta-endorphin during N2O withdrawal might have a significant modulatory effect on transmitter balance, neuronal excitability and corresponding withdrawal behaviour. Furthermore, the decrease of beta-endorphin levels in the whole brain during N2O withdrawal might contribute to the postanaesthesia N2O-excitatory syndrome in humans. This might explain the known therapeutic effect of the opioid drug, meperidine on the excitatory N2O withdrawal phenomena during recovery from N2O anaesthesia in man.


Assuntos
Encéfalo/metabolismo , Óxido Nitroso/efeitos adversos , Síndrome de Abstinência a Substâncias/metabolismo , beta-Endorfina/metabolismo , Animais , Câmaras de Exposição Atmosférica , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos
5.
Int Clin Psychopharmacol ; 4(3): 217-28, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2571635

RESUMO

The biological treatment of depression includes administration of psychoactive drugs (cyclic antidepressants, MAO-inhibitors, neuroleptics and lithium), use of certain substances which in small amounts are normally present in food such as, L-tryptophan (L-TP) and L-5-hydroxytryptophan (L-5HTP), electroconvulsive therapy (ECT) and various manipulations of the sleep-wake rhythms. This paper reviews the literature on the efficacy of these treatments in patients resistant to earlier adequate treatment(s) with cyclic antidepressants. Subsequently the following strategy for the biological treatment of (non-psychotic) major depression is suggested: (1) administration of a cyclic antidepressant; (2) if after a period of 4 to 6 weeks a patient has not responded to an adequate dose, another cyclic antidepressant should be tried, adding lithium if the patient still does not respond; (3) MAO-inhibitors and (4) ECT. In psychotic depression the suggestions for the first, third and fourth steps are the same. In the second step, the cyclic antidepressant should be combined with a neuroleptic.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Depressão/tratamento farmacológico , Antipsicóticos/uso terapêutico , Depressão/dietoterapia , Depressão/terapia , Eletroconvulsoterapia , Lítio/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Privação do Sono
6.
Acta Psychiatr Scand ; 78(6): 668-75, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3146890

RESUMO

Antidepressants are ineffective in about 30% of patients with major depression. Some authors then advise treatment of non-responders with (non-tricyclic) more selective reuptake inhibitors. In a double-blind, partial crossover study, 71 patients were selected for treatment during 4 weeks with oxaprotiline and/or fluvoxamine, two non-tricyclic antidepressants that are selective reuptake inhibitors or noradrenaline and serotonin respectively. All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode. Only 13% of the patients responded, with 27% of them responding to oxaprotiline and none to fluvoxamine. Moreover, a low response of 27% was also obtained in the crossover phase, which included all non-responders to the first treatment, oxaprotiline being effective in 39% and fluvoxamine in 10% of the patients. The results indicate that selective reuptake inhibitors are not an effective alternative for non-responders to other cyclic antidepressants and that non-responders to "noradrenergic" antidepressants do not appear to have much chance of responding to "serotonergic" antidepressants and vice versa.


Assuntos
Antracenos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Maprotilina/uso terapêutico , Oximas/uso terapêutico , Adulto , Transtorno Bipolar/psicologia , Transtorno Depressivo/psicologia , Método Duplo-Cego , Feminino , Fluvoxamina , Humanos , Masculino , Maprotilina/análogos & derivados , Pessoa de Meia-Idade , Transtornos da Personalidade/tratamento farmacológico , Testes Psicológicos , Psicometria
7.
Acta Psychiatr Scand ; 78(6): 676-83, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3146891

RESUMO

Antidepressants are ineffective in about 30% of the patients with major depression. Besides electroconvulsive therapy (ECT) and lithium, MAO inhibitors have been suggested as an alternative in such patients. In 2 controlled, partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants, the effect of the MAO inhibitor tranylcypromine was studied. The first study was an open comparison with L-5-hydroxytryptophan (L-5HTP), the second study a double-blind comparison with nomifensine. Neither the patients treated with L-5HTP nor the patients treated with nomifensine, except one, improved. In contrast, tranylcypromine was effective in 50% of the patients. The depressions of the responders to tranylcypromine appeared to be more endogenous (according Newcastle Scale II) and of shorter duration than those of the non-responders. It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants.


Assuntos
5-Hidroxitriptofano/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Nomifensina/uso terapêutico , Tranilcipromina/uso terapêutico , Adulto , Idoso , Ensaios Clínicos como Assunto , Transtorno Depressivo/psicologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos , Feminino , Fluvoxamina , Humanos , Masculino , Maprotilina/análogos & derivados , Maprotilina/uso terapêutico , Pessoa de Meia-Idade , Oximas/uso terapêutico , Testes Psicológicos
8.
Neuroscience ; 22(1): 233-6, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2888045

RESUMO

Intracerebroventricular administration of phelorphan (158 nmol/2 microliters), a blocker of dipeptidylaminopeptidase (enkephalinase B) and other enzymes involved in the enkephalin biodegradation, inhibited in chronic morphine-dependent rats, the occurrence of some of the naloxone-precipitated withdrawal symptoms. This effect of phelorphan was compared with an equimolar dose of the dipeptidyl-carboxypeptidase inhibitor (enkephalinase A), thiorphan. The results indicate that both drugs decrease some of the naloxone-precipitated withdrawal symptoms (writhing, digging, head hiding, chewing, diarrhoea and Straub tail), while others were potentiated (penile licking) or unaltered (wet dog shakes, grooming and rearing). In addition, phelorphan compared with the controls or thiorphan, pretreated animals, increased the frequency of paw tremor, head shakes, scratching, erection and ejaculation, but other symptoms were decreased (stretching) or unaltered (teeth chattering). The results are discussed in light of the differences in permeability and specificity of the two enkephalinase inhibitors. Furthermore, these data support the hypothesis that the use of enkephalinase inhibitors might be a promising way for the attenuation of the severity of the withdrawal syndrome.


Assuntos
Dipeptídeos/farmacologia , Encefalinas/fisiologia , Dependência de Morfina/fisiopatologia , Inibidores de Proteases/farmacologia , Receptores Opioides/fisiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Aminopeptidases/antagonistas & inibidores , Animais , Encéfalo/fisiopatologia , Antígenos CD13 , Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Endopeptidases , Masculino , Naloxona/farmacologia , Neprilisina , Ratos , Ratos Endogâmicos , Tiorfano , Tiopronina/análogos & derivados , Tiopronina/farmacologia
9.
Gen Pharmacol ; 18(1): 103-5, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3549428

RESUMO

In this study we examined the effects of the enkephalinase inhibitor, thiorphan, on the naloxone-precipitated withdrawal syndrome in chronic morphine dependent rats. Intracerebroventricular administration of thiorphan (40 micrograms/2 microliter) in morphine dependent rats, inhibited the severity of the naloxone-precipitated abstinential syndrome. Administration of thiorphan (20 micrograms/0.5 microliter) in the periaqueductal grey matter of morphine dependent rats, in addition to explosive motor behaviour and ipsilateral rotation, also significantly suppressed most of the naloxone-precipitated withdrawal symptoms. It is suggested that a decreased biotransformation of endogenous opioid peptides might replace the relative shortage of morphine during withdrawal in opiate addicted subjects and attenuate the abstinence symptoms.


Assuntos
Aminoácidos Sulfúricos/farmacologia , Naloxona/antagonistas & inibidores , Inibidores de Proteases/farmacologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Tiopronina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Endopeptidases/metabolismo , Injeções , Injeções Intraventriculares , Masculino , Dependência de Morfina/fisiopatologia , Naloxona/efeitos adversos , Neprilisina , Substância Cinzenta Periaquedutal , Ratos , Ratos Endogâmicos , Síndrome de Abstinência a Substâncias/etiologia , Tiorfano , Tiopronina/análogos & derivados
10.
Pharmacology ; 34(2-3): 61-5, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3035587

RESUMO

We examined the effect of opioid receptor antagonists on the seizure phenomena induced by specific delta opioid receptor agonist [D-Ser2,Leu5] enkephalyl-Thr (DSLET). The experiments have been performed in the anesthetized rats, and the DSLET-induced seizure phenomena were registered by electrocorticogram and electromyogram. It was demonstrated that two selective delta opioid receptor antagonists, ICI 152,129 and ICI 174,864 inhibited DSLET-induced epileptiform ECoG pattern and myoclonic contractions in a dose-related manner. An equimolar concentration of naloxone failed to antagonize the epileptiform effects of DSLET. It is concluded that delta opioid receptor agonist-induced seizure is mediated by delta receptors, since it can be blocked by delta opioid receptor antagonists. Evidently, delta opioid antagonists can be used as a good tool, in order to demonstrate a delta component in the seizure phenomena induced by other endogenous opioid peptides or their derivatives.


Assuntos
Encefalina Leucina/análogos & derivados , Antagonistas de Entorpecentes/farmacologia , Oligopeptídeos/farmacologia , Receptores Opioides/efeitos dos fármacos , Convulsões/induzido quimicamente , Animais , Masculino , Ratos
11.
Arch Int Pharmacodyn Ther ; 283(2): 222-8, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3539055

RESUMO

The effect of the enkephalinase inhibitor phosphoramidon on the withdrawal syndrome following acute and chronic morphine-induced physical dependence in mice, was investigated. Phosphoramidon administered intracerebroventricularly (50-200 micrograms) suppressed significantly the naloxone-precipitated withdrawal jumping and wet dog shakes while forelimb shakes were potentiated in both acute and chronic morphine-dependent mice. It is suggested that increased saturation of the opioid receptors by endogenous opioid peptides following enkephalinase inhibition, might suppress the severity of the withdrawal syndrome.


Assuntos
Comportamento Animal/efeitos dos fármacos , Glicopeptídeos/farmacologia , Dependência de Morfina/psicologia , Naloxona/antagonistas & inibidores , Inibidores de Proteases , Animais , Endopeptidases , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos , Neprilisina , Síndrome de Abstinência a Substâncias/psicologia
12.
Neuropharmacology ; 25(4): 361-5, 1986 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3012398

RESUMO

Blood flow, determined by the radioactive microsphere technique during epileptiform seizures induced by [D-Ser2,Leu5]enkephalyl-Thr (DSLET), a specific delta-opioid receptor agonist, was examined in different areas of the brain of the rat at various time intervals. An increase in blood flow to the hippocampus and brain stem was observed 2.5 min after administration of DSLET into the left lateral ventricle. An additional increase in flow occurred in the striatum and cerebellum 2.5 min later (5 min after the injection), at which time both the neural and vascular effects of the drug were most marked. Ten minutes after the administration of the drug, cerebral blood flow in all regions except the hippocampus, returned to the respective baseline values. Since the time-course and the magnitude of functional activity and blood flow in the hippocampus showed a good correlation, it is suggested that this region of the brain may play an essential role in triggering and maintaining the seizure phenomena induced by enkephalin.


Assuntos
Encéfalo/irrigação sanguínea , Encefalina Leucina/análogos & derivados , Epilepsia/fisiopatologia , Oligopeptídeos/farmacologia , Animais , Pressão Sanguínea , Cerebelo/irrigação sanguínea , Epilepsia/induzido quimicamente , Frequência Cardíaca , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos , Receptores Opioides/efeitos dos fármacos , Receptores Opioides delta
13.
Brain Res ; 302(1): 111-5, 1984 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-6329455

RESUMO

The glucose utilization during specific delta opiate agonist-induced epileptiform phenomena, determined by the [14C]2-deoxyglucose technique (2-DG), was examined in various rat brain areas at different time intervals. The peak in EEG spiking response and the most intensive 2-DG uptake occurred 5 min after intraventricular (i.v.t.) administration of the delta opiate receptor agonist. The most pronounced 2-DG uptake at this time interval can be observed in the subiculum, including the CA1 hippocampal area, frontal cortex and central amygdala. A general decrease of glucose consumption, compared to control values, is observed after 10 min, in all regions, with exception of the subiculum. Since functional activity and 2-DG uptake are correlated, we suggest that the subiculum and/or CA1 area, are probably the brain regions most involved in the enkephalin-induced epileptic phenomena.


Assuntos
Encéfalo/metabolismo , Desoxiaçúcares/metabolismo , Desoxiglucose/metabolismo , Encefalina Leucina/análogos & derivados , Oligopeptídeos/toxicidade , Receptores Opioides/fisiologia , Convulsões/metabolismo , Animais , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Radioisótopos de Carbono , Eletroencefalografia , Cinética , Masculino , Ratos , Ratos Endogâmicos , Receptores Opioides delta , Convulsões/fisiopatologia
14.
Neuropharmacology ; 22(8): 1021-8, 1983 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6353264

RESUMO

The correlation between the distribution of the intraventricularly (i.v.t.) administered delta agonist [3H](D-ala2,D-leu5)-enkephalin ([3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 microns. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of delta opiate receptors, localized within the first 100 microns of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.


Assuntos
Encéfalo/efeitos dos fármacos , Encefalina Leucina/análogos & derivados , Convulsões/induzido quimicamente , Animais , Autorradiografia , Encéfalo/metabolismo , Difusão , Encefalina Leucina/metabolismo , Encefalina Leucina/farmacologia , Leucina Encefalina-2-Alanina , Potenciais Evocados/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos , Convulsões/metabolismo
15.
Naunyn Schmiedebergs Arch Pharmacol ; 322(1): 38-41, 1983 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6405286

RESUMO

The relationship between deprenyl (MAO-B inhibitor), beta-phenylethylamine (PEA, MAO-B substrate) and [D-Ala2]-Met-enkephalinamide (DALA)-induced seizure was studied in the urethane-anaesthetized rats. A combined electromyographic (EMG) and electrocorticographic (ECoG) method was used. PEA (20-100 micrograms ivt) or DALA (10 micrograms ivt) induced myoclonic contractions (MC) in the submandibular muscle and epileptiform pattern with spike activity in the ECoG. Administration of subconvulsant doses of PEA (5-10 micrograms ivt 0.5-1 min before DALA) significantly increased DALA-induced seizure activity. Similarly, blockade of MAO-B with deprenyl (3-48 mg/kg ip) also enhanced DALA-induced epileptiform pattern. It is evident from this study that MAO-B system significantly modulates the excitatory phenomena induced by DALA. These findings of interactions between MAO-B system and enkephalinergic one, might be of relevance in the clinical situations such as psychosis, stress, a use of tricyclic antidepressants and all other cases, where the alteration of MAO-B system is a part of disease or induced during drug therapy.


Assuntos
2-Hidroxifenetilamina/farmacologia , Encefalina Metionina/análogos & derivados , Fenetilaminas/farmacologia , Convulsões/induzido quimicamente , Selegilina/farmacologia , Animais , Sinergismo Farmacológico , Eletroencefalografia , Eletromiografia , Encefalina Metionina/farmacologia , Masculino , Ratos , Ratos Endogâmicos
16.
J Neural Transm ; 57(1-2): 1-11, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6619826

RESUMO

By using electroencephalographic (EEG) and electromyographic recordings in anaesthetized and free-moving rats, two opioid peptides, known as selective agonists for mu and delta opiate receptors, respectively, were examined for their epileptogenic properties. The delta receptor peptide (DSTLE, 4.6-18.6 nmol, intraventricularly, ivt), a putative delta opiate agonist, produced a dose-related increase of myoclonic contractions (MC) with epileptic discharges in anaesthetized rats and severe wet dog shakes, with occasionally falling down, in free-moving animals. Morphiceptin, a specific mu opiate agonist, used in equimolar doses and under the same experimental conditions, had a significantly less pronounced effect on the number of MC and epileptiform EEG phenomena. Similarly, DSTLE (18.6 nmol) injected in the CA2 area of the hippocampus, a region with a nearly equal distribution of mu and delta opiate receptors, induced epileptic discharges in anaesthetized and free-moving rats, while an equimolar dose of morphiceptin had no significant effect. It is suggested that the epileptiform activity of opioid peptides is mainly due to an activation of delta opiate receptors in the central nervous system.


Assuntos
Convulsivantes , Endorfinas/farmacologia , Encefalina Leucina/análogos & derivados , Oligopeptídeos/farmacologia , Convulsões/induzido quimicamente , Animais , Interações Medicamentosas , Endorfinas/administração & dosagem , Hipocampo , Injeções , Injeções Intraventriculares , Masculino , Oligopeptídeos/administração & dosagem , Ratos , Ratos Endogâmicos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...