RESUMEN
The combination of venlafaxine and tramadol was compared with the single use of these agents to investigate the antinociceptive effect on paw withdrawal latency (PWL) to paw pressure in rats with neuropathic pain. Rats were divided into 4 groups: group 1 received saline (0.2 ml i.p.); group 2 received venlafaxine (22 mg/kg i.p.); group 3 received tramadol (20 mg/kg i.p.); and group 4 received venlafaxine + tramadol. No statistically significant changes were observed in the saline and venlafaxine groups with respect to PWL in the lesioned paw. However, tramadol produced a significant antinociceptive effect on the lesioned paw at 30 min compared with the saline and venlafaxine groups. A more potent antinociceptive effect was observed in the tramadol + venlafaxine group, beginning at 60 min and lasting for 1 h. The combination of venlafaxine + tramadol was more effective in increasing the pain threshold in this animal model of neuropathic pain than either of these drugs administered alone.
Asunto(s)
Analgésicos/farmacología , Ciclohexanoles/farmacología , Neuropatía Ciática/tratamiento farmacológico , Tramadol/farmacología , Animales , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Umbral del Dolor/efectos de los fármacos , Presión , Ratas , Ratas Sprague-Dawley , Neuropatía Ciática/fisiopatología , Clorhidrato de VenlafaxinaRESUMEN
Agmatine is an endogenous polyamine metabolite formed by decarboxylation of L-arginine. In this study, the effect of agmatine on tonic pain was compared to its effect on phasic pain by using the formalin and tail-flick (TF) tests in mice. When administered intraperitoneally (ip), agmatine (37.5-300 mg/kg) exhibited a decrease in nociceptive behaviours in the first and second phase of the formalin test, which is a tonic pain model. The alpha(2) adrenoceptor antagonist yohimbine blocked the effect of agmatine in Phase 2 but did not change its effect in Phase 1. In the TF test, there was no significant change in the behaviour of agmatine-administered (75-300 mg/kg) animals. As a result, agmatine appears to have an analgesic effect on tonic rather than phasic pain, and alpha(2) receptors seem partly to have a role in the antinociceptive effect of agmatine on tonic pain.
Asunto(s)
Agmatina/farmacología , Analgésicos/farmacología , Dimensión del Dolor/efectos de los fármacos , Agmatina/administración & dosificación , Analgésicos/administración & dosificación , Animales , Formaldehído , Inyecciones Intraperitoneales , Masculino , Ratones , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Receptores Adrenérgicos alfa 2/efectos de los fármacosRESUMEN
1. Vascular contractile and relaxant responses were evaluated in isolated aortic rings of adjuvant-induced arthritic rats in comparison with control rats, and the effect of an antioxidant treatment on the development of the arthritis was investigated by vitamin E administration (100 mg/kg/day, i.m., for 26 days). 2. Arthritis was induced by an intradermal injection of Freund's complete adjuvant into rat paw. Vascular responses, arthritic lesions and serum copper levels were evaluated after 26 days from adjuvant inoculation. 3. Serum copper levels were significantly lower in arthritic rats than in the control. 4. The contractile response of aortic rings to phenylephrine (PE), but not to KCl, was increased in preparations from arthritic rats, which could be explained by an enhancement of intracellular calcium contents. 5. Acetylcholine (Ach)-mediated endothelium-dependent and sodium nitroprusside (SNP)-mediated endothelium-independent relaxations were not changed significantly in vascular preparations from arthritic rats. 6. In arthritic rats, vitamin E treatment improved arthritic lesions with an increase in copper levels. Despite this ameliorating effect, vitamin E treatment caused an increase in contractile response to PE and a decrease in the relaxant response to Ach and SNP in arthritic rats. 7. These data show that vitamin E provides ameliorating effects in improving systemic signs of experimental arthritis, but it fails to restore abnormalities in vascular function, indicating that adjuvant-induced alterations in vascular function may include mechanisms other than oxygen-free radical formation.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Artritis Experimental/tratamiento farmacológico , Depuradores de Radicales Libres/uso terapéutico , Vitamina E/uso terapéutico , Análisis de Varianza , Animales , Cobre/sangre , Evaluación Preclínica de Medicamentos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nitroprusiato/farmacología , Fenilefrina/farmacología , Ratas , Valores de Referencia , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
In this study, the effect of propofol on isolated bovine coronary artery tone was studied in artery rings precontracted with PGF2a. Propofol, in concentrations of 10-6-10-5 M did not change vascular smooth muscle tone, but at high concentrations (10-4-10-1 M) produced relaxation in rings with intact endothelium. In rings denuded of endothelium or treated with methylene blue, propofol produced relaxation at 10-3-10-1 M concentrations, but there was a significant decrease in relaxation compared to endothelium intact rings. In the presence of a calcium agonist (Bay K 8644; 10-5 M), propofol produced constriction in rings denuded of endothelium. These results suggest that high concentrations of propofol may have vasorelaxant effect on bovine coronary artery and that these effects may be due to actions on the endothelium and mediated by calcium channels.
Asunto(s)
Anestésicos Intravenosos/farmacología , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/fisiología , Propofol/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Bovinos , Vasos Coronarios/fisiología , Técnicas In Vitro , Óxido Nítrico/fisiología , Vasodilatación/efectos de los fármacosRESUMEN
1. Isolated human platelets were used to investigate the effect of atrial natriuretic peptide (ANP) on in vitro platelet aggregation induced by epinephrine, ADP, collagen and 5-hydroxytryptamine. As a direct stimulant of particulate guanylate cyclase, ANP is known to have no direct effect on platelets which contain soluble guanylate cyclase. 2. In our experiments ANP inhibited epinephrine- and partially ADP-induced aggregation in vitro and this effect was suggested to be the result of an interaction of the peptide with adenylate cyclase in platelets. However, the concentrations required to produce this effect were higher than those expected to be found in the circulation both physiologically and pathologically. 3. We therefore conclude that though the peptide may inhibit-aggregation via adenylate cyclase activation, it is unlikely that ANP may play a direct role in preventing platelets aggregating.