Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jul 2013
Antihyperalgesic effects of a novel muscarinic agonist (LASSBio-873) in spinal nerve ligation in rats.
New chemicals or adjuvants with analgesic effects on chronic pain are needed and clinically relevant due to the limited number of effective compounds that possess these characteristics. LASSBio-873, a pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivative, activates muscarinic cholinergic receptors and has potent analgesic effects on acute and inflammatory pain. The present study evaluated the therapeutic and prophylactic effects of oral administration of LASSBio-873 in a spinal nerve ligation (SNL) model of chronic peripheral nerve injury. ⋯ LASSBio-873 treatment did not alter rat behaviour in open field testing measured during the first 24 h after administration and again after 7 continuous days administration. The analgesic effect of LASSBio-873 was inhibited by intrathecal methoctramine, an M2 receptor antagonist, implicating the muscarininc M2 receptor signalling pathway in the drug's action. These results reinforce the potential of LASSBio-873 as a possible prototype for the development of more effective alternatives for the treatment of neuropathic pain.
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Clin. Exp. Pharmacol. Physiol. · Jul 2013
ReviewTicagrelor: positive, negative and misunderstood properties as a new antiplatelet agent.
Dual antiplatelet therapy is essential for the management of acute coronary syndrome. In particular, combination therapy using aspirin with a platelet ADP (i.e. P2Y12 ) receptor inhibitor, such as clopidogrel, prasugrel or, more recently, ticagrelor, has been recommended for patients with acute coronary syndrome. ⋯ Recent studies into ticagrelor report conflicting data, with certain aspects of its mechanisms of action still not fully understood. Ticagrelor has beneficial effects following its clinical application, such as achieving overall higher reductions in mortality compared with the use of clopidogrel and prasugrel. Harmful effects associated with the use of ticagrelor include a higher incidence of dyspnoea and major bleeding compared with clopidogrel.
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Clin. Exp. Pharmacol. Physiol. · Jul 2013
Non-invasive cardiovascular profiling using combined electrocardiogram-Doppler ultrasonography and impedance cardiography: An experimental approach.
In the present study, the feasibility of cardiovascular profiling using both combined electrocardiogram (ECG)-Doppler ultrasonography and impedance cardiography (ICG) was evaluated. Fourteen non-pregnant healthy women received 500 mL saline solution (NaCl 0.9% at 999 mL/h) intravenously by steady state infusion. Before and after this acute volume loading, we measured orthostatic-challenged cardiac and arterial characteristics using ICG and assessed venous characteristics by combined ECG-Doppler before and during the Valsalva manoeuvre. ⋯ Volume loading raised the thoracic fluid content index in both the supine and standing positions (7 ± 2% and 10 ± 1%, respectively; P ≤ 0.014). Combined ECG-Doppler ultrasonography and ICG enables the non-invasive identification of concomitant haemodynamic changes at the level of the heart, the arterial bed and the venous compartment. Our data support the view that non-invasive cardiovascular profiling is feasible, which seems particularly useful for the evaluation of patients who are not critically ill, such as pregnant women.