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91.
两面针结晶8的解痉和镇痛作用研究 总被引:15,自引:0,他引:15
结晶-8,是从两面针提出的一种单体。当浓度为1×10-6~1×10-4g/ml对正常离体豚鼠回肠活动无影响,但对乙酰胆硷、匹鲁卡品、氯化钡及组织胺所致肠肌收缩有明显的松弛作用;结晶-8腹腔注射10 mg/kg有明显抑制小鼠扭体反应;8~20 mg/kg明显提高家兔及大鼠痛阈,200μg/kg脑室注射亦有明显提高大鼠痛阈。其镇痛作用不被丙烯吗啡(5 mg/kg)所拮抗,而被利血平(4 mg/kg)所对抗。表明结晶-8的解痉作用直接作用于肠平滑肌。而镇痛作用具有中枢性,与吗啡受体无直接关系,但与脑内单胺类介质有关。 相似文献
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93.
Angélica M. Teixeira Liz Müller Daniel H. Roos Marilise E. Bürger 《Pharmacology, biochemistry, and behavior》2009,92(2):231-235
Regular physical activity exerts beneficial effects for mental and physical health, but an intense exercise can cause oxidative stress (OS) in dopaminergic regions and intensify the harmful effects of reserpine. Reserpine-induced neurotoxicity can be accessed by behavioral and biochemical evaluations. The objective of this study was to examine the effect of a gradual intensifying exercise program on an animal model of oxidative stress. Male rats were submitted to swimming sessions (1 h/day, for eleven weeks), and they were loaded gradually during the adaptation period (two weeks) with a weight corresponding to 1-7% of their body weight tied to their back. After the last training, the animals were treated with two doses of vehicle or reserpine (1 mg/kg-sc), an agent that induces orofacial dyskinesia. After behavioral evaluations, the striatum was dissected for enzymatic and biochemical assays. Development of cardiac hypertrophy demonstrated the effectiveness of the physical training. The gradual intense exercise and reserpine increased lipid peroxidation and striatal catalase activity. The results confirm the importance of catalase activity in orofacial dyskinesia which can be related to lipid peroxidation in striatal dopaminergic brain tissue. These results indicate that intense exercise can have some deleterious effect on striatal dopaminergic system. 相似文献
94.
The role of D(3) receptors in the antiparkinsonian actions of l-DOPA and l-DOPA-induced dyskinesia (LID) remains unclear. The D(3) receptor partial agonist BP897 attenuates LID in primates without affecting the antiparkinsonian actions of l-DOPA, suggesting that "normalization" of D(3) activity is antidyskinetic [Bezard, E., Ferry, S., Mach, U., Stark, H., Leriche, L., Boraud, T., Gross, C., and Sokoloff, P., 2003. Attenuation of levodopa-induced dyskinesia by normalizing dopamine D(3) receptor function. Nat. Med. 9, 762-767]. However, subsequent studies have questioned these findings [Hsu, A., Togasaki, D.M., Bezard, E., Sokoloff, P., Langston, J.W., Di Monte, D.A., and Quik, M., 2004. Effect of the D(3) dopamine receptor partial agonist BP897 [N-[4-(4-(2-methoxyphenyl)piperazinyl)butyl]-2-naphthamide] on l-3,4-dihydroxyphenylalanine-induced dyskinesias and parkinsonism in squirrel monkeys. J. Pharmacol. Exp. Ther. 311, 770-777]. The D(3) receptor antagonist S33084 is not antidyskinetic yet enhances the antiparkinsonian actions of l-DOPA, suggesting that stimulation of D(3) receptors is not involved in LID. Here, we address the possibility that in vivo BP897 acts via mechanisms in addition to attenuation of D(3) signaling. l-DOPA (125 mg/kg) elicits hyperkinesia in reserpine-treated rats, the vertical component of which (rearing) is attenuated by agents with antidyskinetic actions in MPTP-lesioned primates and Parkinson's disease (PD) [Johnston, T.H., Lee, J., Gomez-Ramirez, J., Fox, S.H., and Brotchie, J.M., 2005. A simple rodent assay for the in vivo identification of agents with potential to reduce levodopa-induced dyskinesia in Parkinson's disease. Exp. Neurol. 191, 243-250]. BP897 (0.1, 0.3, 1.0 and 3 mg/kg) reduced l-DOPA-induced rearing by 0%, 44%, 86% and 57% respectively. In contrast, S33084 had no effect on l-DOPA-induced rearing (0.1 mg/kg, 115%; 0.3 mg/kg, 94%, 1 mg/kg, 134%; 3 mg/kg, 100%, of vehicle, all P > 0.05). Furthermore, S33084 failed to antagonize the effects of BP897 on l-DOPA-induced rearing. The influence of BP897 on l-DOPA-induced rearing was, however, mimicked by the selective D(2) antagonist L741,626. Finally, BP897 attenuated l-DOPA-induced horizontal activity, an action attenuated by S33084 and mimicked by L741,626. Thus, while BP897 may reduce LID, we raise the possibility that receptors other than D(3) receptors might be involved in this action. 相似文献
95.
Immunohistochemical study of the serotonergic neuronal system in an animal model of the mood disorder 总被引:3,自引:0,他引:3
The monoamine theory is one of the major hypotheses about the biological etiology of major depressive disorders. Recent pharmacological and postmortem investigations suggest that depressed patients have alterations in function of serotonergic neuronal system. However, the exact sites of alterations and the association between these alterations and the etiology of the disorder are still unclear. To elucidate these issues, we immunohistochemically examined vesicle monoamine transporter 2 (VMAT2), serotonin receptor type 1a (5HT1a), and serotonin transporter (5HTT) in the hippocampal region of reserpine-treated rats, an animal model of depression. The results showed more VMAT2-immunoreactive varicose fibers in the pyramidal cell layer of hippocampus and parahippocampal cortexes, and more intense 5HTT-immunoreactivity in the pyramidal cell layer and the area CA4 of hippocampus in the animal models compared to those of the controls. On the other hand, lower density of 5HT1a-immunoreactive deposits in the pyramidal cell layer of hippocampus and the parahippocampal cortex was observed in the animal models compared to those of the controls. These results suggest that a deficit of monoamines induces the alterations in the expression of the storage protein, the receptor and the transporter that are involved in the serotonergic neurotransmission in the hippocampal region. These alterations may underlie the changes of serotonergic system observed in the brains of patients with the depressive disorder. 相似文献
96.
Castro JP Frussa-Filho R Fukushiro DF Silva RH Medrano WA Ribeiro Rde A Abílio VC 《Brain research bulletin》2006,68(6):436-441
We have described that GABA mimetic drugs present the ability to inhibit the expression of reserpine-induced oral movements. In this respect, oral movements is associated with important neuropathologies. This study investigates the effects of an acute or a repeated treatment of different doses of the GABA(B) agonist baclofen, as well as withdrawal from these treatments, on the development and/or expression of reserpine-induced vacuous chewing movements (VCM). Male mice received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. In the first experiment, 24h later, animals were acutely treated with vehicle or baclofen (1, 2 or 4 mg/kg). In the second experiment, animals were treated with vehicle or baclofen (1 or 4 mg/kg) for four consecutive days receiving a concomitant injection of 1mg/kg reserpine (or vehicle) on Days 2 and 4. Twenty-four hours later, animals received vehicle or baclofen. Thirty minutes after the last injection, they were observed for quantification of VCM and open-field general activity. The acute administration of all the doses of baclofen abolished the manifestation of reserpine-induced VCM. Repeated treatment with 1mg/kg baclofen induced tolerance to the ability of an acute injection of this dose to reduce VCM. Treatment with baclofen (4 mg/kg) did not modify spontaneous VCM. Acute administration of the highest dose induced a decrease in general motor activity and a potentiation of the reserpine-induced decrease in general activity. These results reinforce the involvement of GABAergic hypofunction in the expression of oral movements and suggest that a repeated treatment with baclofen induces compensatory changes in GABAergic transmission that can attenuate its acute property to decrease VCM. 相似文献
97.
98.
99.
A. McGroarty S. A. Greenfield 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1996,110(3):360-366
The substantia nigra has one of the highest levels of ATP-sensitive K+ channel in the brain. Since this channel is controlled by cell metabolism, the aim of this study was to see how closely it is associated with nigral dopamine systems, which are decreased in Parkinson's disease. In a sub-population of neurons within the rostral substantia nigra pars compacta of the guinea-pig, a brief period of hypoxia resulted in a tolbutamide (100–500 M) sensitive hyperpolarisation [input resistance (IR) decrease from 144.88±14.04 M pre-hypoxia to 105.91±13.25 M during hypoxia]. Maximal blockade of this decrease was seen in presence of 500 m tolbutamide [IR decrease only from 161.35±32.82 M to 155.02±34.29 M]. Reserpine (which depletes dopamine stores) but not -methyl-para-tyrosine (which decreases de novo synthesis of dopamine) caused a marked attenuation of this hyperpolarisation [IR decrease only from 163.32±44.42 M pre-hypoxia to 154.42±50.97 M during hypoxia]. This observation suggests that blockade of dopamine storage, but not of de novo synthesis, leads to a loss of responsiveness of certain mid-brain neurons to hypoxia, rendering them potentially more susceptible to subsequent degeneration. The possible link between nigral dopamine systems and ATP-sensitive K+ channels is discussed. 相似文献
100.
U. Kilz J. Schaefer P. A. van Zwieten 《Pflügers Archiv : European journal of physiology》1969,308(3):203-213
Summary In order to establish whether adrenergic mechanisms are involved in frequency induced potentiation and in the positive inotropic response to paired stimulation, the effect of adrenergic drugs on both processes were studied in guineapig isolated left auricles. 1. Owing to the positive inotropic effect of noradrenaline and isoproterenol the relative increase in contractile force at rising frequencies proved less pronounced than in control experiments, although the absolute maximal force that developed was higher in presence of the sympathomimetic drugs. 2. Pretreatment of the guinea-pigs with high doses of reserpine did not impair both potentiation phenomena in the isolated organs. Surprisingly, frequency potentiation proved even slightly increased in the noradrenaline-depleted organs. 3. A low concentration of propranolol (10–9 M) did not affect both potentiation phenomena. Propranolol, in such concentration (10–6 M) that unspecific, quinidine-like effects occurred diminished both frequency potentiation and the response to paired stimulation. 4. The results suggest that adrenergic mechanisms do not play any significant role in both potentiation phenomena. 相似文献