Current and prospective pharmacological targets in relation to antimigraine action

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

Characterizations of Pareto-efficient, fair, and strategy-proof allocation rules in queueing problems

A set of agents with possibly different waiting costs have to receive the same service one after the other. Efficiency requires to maximize total welfare. Fairness requires to treat equal agents equally. One must form a queue, set up monetary transfers to compensate agents having to wait, and not a priori arbitrarily exclude agents from positions. As one may not know agents waiting costs, they may have no incentive to reveal them. We identify the only rule satisfying Pareto-efficiency, equal treatment of equals in welfare or symmetry, and strategy-proofness. It satisfies stronger axioms, as no-envy and anonymity. Further, its desirability extends to related problems. To obtain these results, We prove that a rule, single-valued or not, satisfies queue-efficiency and strategy-proofness if and only if it always selects efficient queues and sets transfers A la Groves [Groves, T., 1973. Incentives in teams. Econometrica 41, 617-631]. This holds in other problems, provided the domain of quasi-linear preferences is rich enough