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1.
Gene ; 806: 145920, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34455026

RESUMO

Depression is deemed a mood disorder characterized by a high rate of relapse. Therefore, overcoming of the recurrent depression is globally expecting. Kososan, a traditional Japanese herbal medicine, has been clinically used for mild depressive mood, and our previous studies have shown some evidence for its antidepressive-like efficacy in experimental animal models of depression. However, it remains unclear whether kososan has beneficial effects on recurrent depression. Here, we examined its effect using a mouse model of modified repeated social defeat stress (SDS) paradigm. Male BALB/c mice were exposed to a 5-min SDS from unfamiliar aggressive CD-1 mice for 5 days. Kososan extract (1.0 kg/kg/day) or an antidepressant milnacipran (60 mg/kg/day) was administered orally for 26 days (days 7-32) to depression-like mice with social avoidant behaviors on day 6. Single 5 min of SDS was subjected to mice recovered from the social avoidance on day 31, and then the recurrence of depression-like behaviors was evaluated on day 32. Hippocampal gene expression patterns were also assayed by DNA microarray analysis. Water- or milnacipran-administered mice resulted in a recurrence of depression-like behaviors by re-exposure of single SDS, whereas kososan-administered mice did not recur depression-like behaviors. Distinct gene expression patterns were also found for treating kososan and milnacipran. Collectively, this finding suggests that kososan exerts a preventive effect on recurrent depression-like behaviors in mice. Pretreatment of kososan is more useful for recurrent depression than that of milnacipran.


Assuntos
Antidepressivos/farmacologia , Depressão/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Proteínas do Tecido Nervoso/genética , Derrota Social , Estresse Psicológico/tratamento farmacológico , Administração Oral , Animais , Depressão/genética , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos , Camundongos Endogâmicos BALB C , Milnaciprano/farmacologia , Anotação de Sequência Molecular , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Recidiva , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia
2.
Inflammopharmacology ; 28(4): 903-913, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32518981

RESUMO

BACKGROUND: Many injuries cause pain and inflammation, which are one of the major challenges for physicians. In this study, the analgesic and the anti-inflammatory effects of milnacipran were investigated on carrageenan-induced nociception and inflammation in male rats. METHODS: Pain and inflammation were induced by injection of λ-carrageenan (1% v/v) into the hind paw. Indomethacin (10 mg/kg: ip) or milnacipran (10, 20 and 40 mg/kg: ip) were administered 30 min before carrageenan. Analgesia and inflammation were measured by hot plate and plethysmometer. Finally, lipid peroxidation, tumor necrosis factor alpha (TNF-α), Interleukin 1 beta (IL-1ß), Interleukin 6 (IL-6), myeloperoxidase (MPO) activity, nitric oxide (NO) and total antioxidant capacity (TAC) status evaluated in the hind paw tissue. RESULTS: The results showed that carrageenan caused hyperalgesia and inflammation in the hind paw tissue. Milnacipran (20 and 40 mg/kg) significantly and dose-dependently attenuated (65 ± 3.2%; p ≤0.01 and 42 ± 6.2%; p ≤ 0.001, respectively) carrageenan-induced inflammation and significantly increased (p ≤ 0.001) nociception threshold. Also, milnacipran (20 and 40 mg/kg) significantly suppressed levels of malondialdehyde (MDA), NO (p ≤ 0.05), MPO activity, TNF-α, IL-1ß and IL-6 (p ≤ 0.001) following carrageenan injection. Additionally, milnacipran (10, 20 and 40 mg/kg) significantly augmented (p ≤ 0.05) TAC status following carrageenan in the hind paw tissue. CONCLUSION: In the present study, milnacipran showed anti-nociceptive and anti-inflammatory effects on carrageenan-induced hyperalgesia and inflammation in a dose-dependent manner. Milnacipran reduced inflammatory edema and increased the paw withdrawal threshold probably through suppression of MDA, NO, TNF-α, IL-1ß, IL-6 and MPO activity, and increase of TAC status in the hind paw tissue. Therefore, milnacipran holds important potential as an anti-inflammatory and anti-nociceptive drug. Although, further clinical trials to confirm this issue, is required.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Milnaciprano/farmacologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Animais , Carragenina/farmacologia , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Indometacina/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
3.
Behav Pharmacol ; 30(6): 463-470, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30724802

RESUMO

Pain is a significant public health problem, and assessment of pain-related impairment of behavior is a key clinical indicator and treatment target. Similar to opioids and NSAIDs, dopamine (DA) transporter inhibitors block pain-related depression of intracranial self-stimulation (ICSS) in rats. The primary goal of the present study was to determine if the effects of monoamine uptake inhibitors on pain-related depression of ICSS in rats extend to an assay of pain-related depression of nesting in mice. We hypothesized that the DA transporter-selective uptake inhibitor bupropion would block depression of nesting behavior produced by intraperitoneal injection of lactic acid, whereas selective serotonin transporter-selective citalopram, norepinephrine transporter-selective nisoxetine, and the mixed action selective serotonin transporter/norepinephrine transporter inhibitor milnacipran would be ineffective. Effects of the NSAID ketoprofen were also obtained to facilitate interpretation of the effects of the monoamine uptake inhibitors. Consistent with previous findings, ketoprofen blocked pain-related depression of nesting. In contrast, none of the monoamine uptake inhibitors blocked pain-related depression of nesting, although they all blocked pain-related stimulation of stretching. Unlike findings from studies of pain-related depression of ICSS, these results do not support consideration of DA uptake inhibitors for treatment of pain-related depression of behavior.


Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento de Nidação/efeitos dos fármacos , Dor/tratamento farmacológico , Analgésicos Opioides/farmacologia , Animais , Bupropiona/farmacologia , Citalopram/farmacologia , Condicionamento Operante/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Fluoxetina/análogos & derivados , Fluoxetina/farmacologia , Cetoprofeno/farmacologia , Ácido Láctico/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Milnaciprano/farmacologia , Receptores Opioides kappa/metabolismo , Receptores Opioides kappa/fisiologia , Autoestimulação/efeitos dos fármacos
4.
Australas Psychiatry ; 26(5): 537-540, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30198305

RESUMO

OBJECTIVE: Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) approved for treatment of fibromyalgia in Australia, but is used for depression in Europe and elsewhere. This paper will briefly review milnacipran and its utility in psychiatry for the treatment of depression. CONCLUSION: Milnacipran is a dual reuptake inhibitor of noradrenaline and serotonin, with greater effect on noradrenaline than serotonin, in contrast to the related drugs venlafaxine, desvenlafaxine and duloxetine. Rapidly absorbed irrespective of food, milnacipran has a half-life of approximately 8 hours, reaches steady state in 2 days and is excreted renally. Milnacipran helps a minority of patients with fibromyalgia by reducing pain and fatigue. It is also an effective antidepressant with efficacy comparable to venlafaxine and duloxetine, and a side effect profile characteristic of SNRIs. The dose range is 50-200 mg, in divided doses. Milnacipran may be useful for patients with depression and pain, and endogenous depression characterised by anergia, psychomotor retardation and hypersomnia. Caution is necessary in the presence of heart disease, hypertension, renal impairment, epilepsy, glaucoma, bipolar disorder, and bleeding tendency. Milnacipran is likely to be a useful late antidepressant option in treatment-resistant patients, as well as those with chronic pain, anergia and hypersomnia.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Fibromialgia/tratamento farmacológico , Milnaciprano/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia , Humanos , Milnaciprano/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem
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