Pharmacological research : the official journal of the Italian Pharmacological Society
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While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. ⋯ In the presence of atropine and guanethidine (NANC conditions) EFS-induced TTX-sensitive relaxation consisting in an early and rapid component followed by a second slow phase, which were unaffected by cannabinoid drugs. In conclusion, the present results suggest that cannabinoids play a prejunctional modulatory role on the cholinergic excitatory transmission without affecting the NANC inhibitory transmission. In addition, this study provides experimental evidence that also the activation of CB2 receptors is able to reduce cholinergic neurotransmission in the mouse stomach.
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In a previous screening work, Foeniculum vulgare essential oil emerged from a pool of 24 essential oils for its antiplatelet properties and its ability to destabilize the retraction of the coagulum. In the present work the main component of the oil, anethole, tested in guinea pig plasma was as potent as fennel oil in inhibiting arachidonic acid-, collagen-, ADP- and U46619-induced aggregation (IC(50) from 4 to 147 microg ml(-1)). It also prevented thrombin-induced clot retraction at concentrations similar to fennel oil. ⋯ At the antithrombotic dosage they were free from prohemorrhagic side effect at variance with acetylsalicylic acid used as reference drug. Furthermore, both F. vulgare essential oil and anethole (100 mg kg(-1) oral administration) provided significant protection toward ethanol induced gastric lesions in rats. In conclusion, these results demonstrate for F. vulgare essential oil, and its main component anethole, a safe antithrombotic activity that seems due to their broad spectrum antiplatelet activity, clot destabilizing effect and vasorelaxant action.
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Comparative Study
Tramadol is more effective than morphine and amitriptyline against ischaemic pain but not thermal pain in rats.
The aim of this study was to compare the analgesic efficacies of tramadol, which acts on opioid receptors and inhibits monoamine reuptake, to amitriptyline, a monoamine reuptake inhibitor as well as to morphine, an opioid receptor agonist. We compared the motor function impairment and response latencies to noxious thermal and noxious ischaemic challenges after tramadol administration to those after morphine and after amitriptyline administration. We injected Sprague-Dawley rats (i.p.) with either tramadol (1, 5, 15 and 25 mg kg(-1)), morphine (0.01, 0.1, 1 and 5 mg kg(-1)) or amitriptyline (1, 3 and 10 mg kg(-1)) and a control injection of saline (100 microl). ⋯ The escape latency against noxious ischaemia after morphine and amitriptyline administration did not change, despite an increase in dose, while increasing doses of tramadol (1-25 mg kg(-1)) provided increasing analgesia against noxious ischaemia. Significant impairment to motor function occurred after morphine (5 mg kg(-1)), tramadol (15 mg kg(-1)) and amitriptyline (10 mg kg(-1)) administration, with only 11, 50 and 38% of animals, respectively, completing the rotarod trial, compared to 100% completion after saline administration. As previously demonstrated, morphine was more potent than tramadol for the relief of thermal pain but tramadol may be a more beneficial drug for relieving severe ischaemic pain.
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Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, and by resistance to insulin's effects. Such a deficiency results in increased concentrations of glucose and other metabolites in the blood, which in turn damages many of the body's systems, in particular the eyes, kidneys, nerves, heart and blood vessels. There are two major types of diabetes mellitus: Type 1 diabetes (insulin-dependent diabetes, IDDM or juvenile onset diabetes) and Type 2 diabetes (non-insulin-dependent diabetes, NIDDM or adult-onset). ⋯ Clinical studies have shown that ruboxistaurin, a PKCbeta isoform selective inhibitor, normalize endothelial dysfunction, renal glomerular filtration rate and prevented loss of visual acuity in diabetic patients. Thus, PKC activation involving several isoforms is likely to be responsible for some of the pathologies in diabetic retinopathy, nephropathy and cardiovascular disease. PKC isoform selective inhibitors are likely new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease with very little side effects.
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These studies were designed to assess the pharmacodynamic interaction between formoterol and beclomethasone dipropionate (BDP) in controlling the bronchoconstriction and inflammatory response induced by various challenges in guinea-pigs and rats. In anaesthetised guinea-pigs, superfusion of the formoterol/BDP combination into the tracheal lumen had significantly more effect than the single components in antagonising the bronchoconstricting and inflammatory responses to acetylcholine or ovalbumin in a standard model of airway hyper-responsiveness. ⋯ Finally, in tracheal strips from ovalbumin-sensitised guinea-pigs pre-treatment with BDP (30 mg kg(-1) i.m.) completely reversed the rightward shift of the formoterol dose-response curve due to beta(2)-receptor desensitisation. In conclusion, these results indicate that formoterol and BDP together induce a favourable pharmacodynamic interaction which can be considered more than additive, at least in these experimental settings.