21 research outputs found

    Current and prospective pharmacological targets in relation to antimigraine action

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    Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

    Heterogeneous distribution of phosphorus in olivine from otherwise well-equilibrated spinel peridotite xenoliths and its implications for the mantle geochemistry of lithium

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    The major- and trace-element abundances of the coexisting phases of four metasomatized spinel peridotite xenoliths from the Anakies locality (SE Australia) were determined by electron microprobe and laser-ablation ICP-MS. The compositions of all phases are remarkably homogeneous, with the exception of phosphorus (P), lithium (Li) and sodium (Na) in olivine. These three elements are enriched in large parts of most olivine crystals due to a second metasomatic episode. Apart from these elements, all phases are in mutual equilibrium with respect to both their major- and trace-element compositions. Li and Na show a strong correlation with P in olivine, although molar Li + Na are an order of magnitude less than molar P, indicating that the substitution mechanism of these elements is more complex than the simple charge-balanced coupled exchange IVSi 4+ + VI(FeMg) 2+ = IVP 5+ + VI(LiNa) +. We suggest that Li and Na are decorating octahedral-site cation vacancies formed by the original incorporation of P. Elemental maps revealed that the P zoning patterns are concentric in a few large olivine porphyroblasts, but form irregular patches in most crystals. This distribution of P is proposed to be the result of a two-stage process, whereby the initial concentric zoning, caused by its exceptionally sluggish diffusion after metasomatic influx, is broken up by extensive sub-solidus deformation and recrystallization, attesting to large grain-scale strains even within the lithosphere. Such strains must be an efficient means of ensuring trace-element equilibrium during partial melting. The association of Li with P in olivine may help to explain the variability of Li abundances in mantle minerals and to interpret Li diffusion experiments and Li isotopic fractionation
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