RESUMO
Pain has a negative impact on public health, reducing quality of life. Unfortunately, current treatments are not fully effective and have adverse effects. Therefore, there is a need to develop new analgesic compounds. Due to promising results regarding the antinociceptive effect of N-(3-(phenylselanyl)prop-2-in-1-yl)benzamide (SePB), this study aimed to evaluate the participation of the dopaminergic and noradrenergic systems in this effect in mice, as well as its toxicity. To this, the antagonists sulpiride (D2/D3 receptor antagonist, 5 mg/kg), SCH-23390 (D1 receptor antagonist, 0.05 mg/kg), prazosin (α1 adrenergic receptor antagonist, 0.15 mg/kg), yohimbine (α2-adrenergic receptors, 0.15 mg/kg) and propranolol (non-selective ß-adrenergic antagonist, 10 mg/kg) were administered intraperitoneally to mice 15 min before SePB (10 mg/kg, intragastrically), except for propranolol (20 min). After 26 min of SePB administration, the open field test was performed for 4 min to assess locomotor activity, followed by the tail immersion test to measure the nociceptive response. For the toxicity test, animals received a high dose of 300 mg/kg of SePB. SePB showed an increase in the latency for nociceptive response in the tail immersion test, and this effect was prevented by SCH-23390, yohimbine and propranolol, indicating the involvement of D1, α2 and ß-adrenergic receptors in the antinociceptive mechanism of the SePB effect. No changes were observed in the open field test, and the toxicity assessment suggested that SePB has low potential to induce toxicity. These findings contribute to understanding SePB's mechanism of action, with a focus on the development of new alternatives for pain treatment.
Assuntos
Propranolol , Qualidade de Vida , Camundongos , Animais , Propranolol/farmacologia , Propranolol/uso terapêutico , Analgésicos/toxicidade , Dor/tratamento farmacológico , Norepinefrina , Ioimbina/toxicidade , Ioimbina/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Dopamina , Sulpirida , Receptores Adrenérgicos alfa 2RESUMO
Animal studies reveal that diverse environmental stimuli that generate anxiety-like behaviors also induce antinociception; conversely, clinical data show that pain perception is reduced under anxiolysis. This study was conducted to investigate the influence of pharmacologically induced-anxiety on nociception and antinociception. Experimental anxiety levels were measured using the rat burying behavior test. Diazepam (0, 0.5, 1.0 and 2.0 mg/kg, i.p.) or yohimbine (0, 0.5 and 1.0 mg/kg, i.p.) were used as anxiolytic or anxiogenic drugs, respectively. To evaluate the influence of different experimental anxiety levels on nociception, the pain-induced functional impairment in the rat (PIFIR model) was used. Nociception was induced by an intra-articular injection of 15% uric acid into the knee joint of the right hind limb. Diazepam or yohimbine were administered 15 min before uric acid and the ability of the rat to use the injured hind limb was recorded. To analyze the influence of different levels of anxiety on the antinociceptive effects produced by acetylsalicylic acid (0, 31, 100 and 310 mg/kg, p.o.); this analgesic was administered 3.5 h after uric acid. Fifteen min before diazepam (2.0 mg/kg) or yohimbine (1.0 mg/kg) were administered. We found that, in the burying behavior test, diazepam and yohimbine produced a dose-dependent decrease or augment in the cumulative time of burying, effects denoting reduced or increased experimental anxiety, respectively. Diazepam or yohimbine, administered alone, was unable to produce nociception. The results showed an influence of anxiety on nociception since a decreased (by diazepam) or increased (by yohimbine) experimental anxiety prevented nociception. Control experiments showed that acetylsalicylic acid did not modify experimental anxiety in the burying behavior test, but effectively reversed the nociception induced by uric acid (15%) in the PIFIR model. Such antinociceptive effect was unmodified by the anxiolytic or anxiogenic actions of diazepam or yohimbine. Data are discussed on the bases of clinical- and animal-studies revealing interactions between anxiety and nociception.
Assuntos
Ansiedade/fisiopatologia , Diazepam/farmacologia , Dor/prevenção & controle , Dor/fisiopatologia , Ioimbina/farmacologia , Análise de Variância , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Ansiolíticos/toxicidade , Ansiedade/induzido quimicamente , Aspirina/farmacologia , Comportamento Animal/efeitos dos fármacos , Diazepam/administração & dosagem , Diazepam/toxicidade , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Masculino , Dor/induzido quimicamente , Ratos , Ratos Wistar , Fatores de Tempo , Ioimbina/administração & dosagem , Ioimbina/toxicidadeRESUMO
In the last decade, the possible correlation between the use of reserpine and rauwolfia drugs as antihypertensive agents and breast cancer incidence has been investigated. For the purpose of evaluating the mutagenic and genotoxic effects of these drugs, reserpine and ajmalicine were studied using the SOS Chromotest and the induction of gene conversion, crossing-over and reverse mutation in the yeast diploid strain XS2316. The results indicated a lack of genotoxic, mutagenic and recombinogenic effects.