Dihydroergotamine, ergotamine, methysergide and sumatriptan - Basic science in relation to migraine treatment

The 5-hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT 1B, 5-HT1D, and 5-HT1F receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the "triptan" sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these four drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The acute antimigraine efficacy of these remedies is very much dependent on the formulation used where, in general, parenteral formulations are more effective in reliving the symptoms of a migraine attack

Coronary Side Effects of Antimigraine Drugs From Patient to Receptor

Migraine is a paroxysmal neurological disorder, which occurs in 6% of males and 15-18% of females, with the highest prevalence between the ages of 25 and 55 years1,2. Attacks consist of moderate or severe headache, associated with nausea, vomiting, photo- and phonophobia3. The headache lasts 4 to 72 hours and increases with physical activity. The migraine attack may be resolved by sleep during or after the headache4. In about 15% of patients (migraine with aura), an aura may precede the migraine headache within about one hour. The aura usually consists of visual symptoms such as fortifications, scotoma or hemianopsia, but may also be sensory (paresthesia), motor- (weakness, paresis) or speech-related (dysarthria, aphasia)1. To study migraine scientifically, there is a clear need for uniform criteria to determine whether a patient is suffering from a migraine headache. In 1988, the International Headache Society (IHS) provided such criteria5 (see Table 1.1 for migraine without and with aura)

Tunable coupling of qubits: nonadiabatic corrections

We analyze the coupling of qubits mediated by a tunable and fast element beyond the adiabatic approximation. The nonadiabatic corrections are important and even dominant in parts of the relevant parameter range. As an example, we consider the tunable capacitive coupling between two charge qubits mediated by a gated Josephson junction, as suggested by Averin and Bruder. The nonadiabatic, inductive contribution persists when the capacitive coupling is tuned to zero. On the other hand, the total coupling can be turned off (in the rotating wave approximation) if the qubits are operated at symmetry points.Comment: 7 pages, 2 figures, accepted in Europhysics Letter

Approach to the extremal limit of the Schwarzschild-de Sitter black hole

The quasinormal-mode spectrum of the Schwarzschild-de Sitter black hole is studied in the limit of near-equal black-hole and cosmological radii. It is found that the mode_frequencies_ agree with the P"oschl-Teller approximation to one more order than previously realized, even though the effective_potential_ does not. Whether the spectrum approaches the limiting one uniformly in the mode index is seen to depend on the chosen units (to the order investigated). A perturbation framework is set up, in which these issues can be studied to higher order in future.Comment: REVTeX4, 4pp., no figures. N.B. "Alec" is my first, and "Maassen van den Brink" my family name. v2: added numerical verificatio

The need for new acutely acting antimigraine drugs: moving safely outside acute medication overuse

Background: The treatment of migraine is impeded by several difficulties, among which insufficient headache relief, side effects, and risk for developing medication overuse headache (MOH). Thus, new acutely acting antimigraine drugs are currently being developed, among which the small molecule CGRP receptor antagonists, gepants, and the 5-HT1F receptor agonist lasmiditan. Whether treatment with these drugs carries the same risk for developing MOH is currently unknown. Main body: Pathophysiological studies on MOH in animal models have suggested that decreased 5- hydroxytryptamine (5-HT, serotonin) levels, increased calcitonin-gene related peptide (CGRP) expression and changes in 5-HT receptor expression (lower 5-HT1B/D and higher 5-HT2A expression) may be involved in MOH. The decreased 5-HT may increase cortical spreading depression frequency and induce central sensitization in the cerebral cortex and caudal nucleus of the trigeminal tract. Additionally, low concentrations of 5-HT, a feature often observed in MOH patients, could increase CGRP expression. This provides a possible link between the pathways of 5-HT and CGRP, targets of lasmiditan and gepants, respectively. Since lasmiditan is a 5-HT1F receptor agonist and gepants are CGRP receptor antagonists, they could have different risks for developing MOH because of the different (over) compensation mechanisms following prolonged agonist versus antagonist treatment. Conclusion: The acute treatment of migraine will certainly improve with the advent of two novel classes of drugs, i.e., the 5-HT1F receptor agonists (lasmiditan) and the small molecule CGRP receptor antagonists (gepants). Data on the effects of 5-HT1F receptor agonism in relation to MOH, as well as the effects of chronic CGRP receptor blockade, are awaited with interest

Mediated tunable coupling of flux qubits

It is sketched how a monostable rf- or dc-SQUID can mediate an inductive coupling between two adjacent flux qubits. The nontrivial dependence of the SQUID's susceptibility on external flux makes it possible to continuously tune the induced coupling from antiferromagnetic (AF) to ferromagnetic (FM). In particular, for suitable parameters, the induced FM coupling can be sufficiently large to overcome any possible direct AF inductive coupling between the qubits. The main features follow from a classical analysis of the multi-qubit potential. A fully quantum treatment yields similar results, but with a modified expression for the SQUID susceptibility. Since the latter is exact, it can also be used to evaluate the susceptibility--or, equivalently, energy-level curvature--of an isolated rf-SQUID for larger shielding and at degenerate flux bias, i.e., a (bistable) qubit. The result is compared to the standard two-level (pseudospin) treatment of the anticrossing, and the ensuing conclusions are verified numerically.Comment: REVTeX 4, 16 pp., 4 EPS figures. N.B.: "Alec" is my first, and "Maassen van den Brink" my family name. v2: major expansion and rewriting, new title and co-author; to appear in New Journal of Physics special issue (R. Fazio, ed.

Hamiltonian and Linear-Space Structure for Damped Oscillators: I. General Theory

The phase space of $N$ damped linear oscillators is endowed with a bilinear map under which the evolution operator is symmetric. This analog of self-adjointness allows properties familiar from conservative systems to be recovered, e.g., eigenvectors are "orthogonal" under the bilinear map and obey sum rules, initial-value problems are readily solved and perturbation theory applies to the_complex_ eigenvalues. These concepts are conveniently represented in a biorthogonal basis.Comment: REVTeX4, 10pp., 1 PS figure. N.B.: `Alec' is my first name, `Maassen van den Brink' my family name. v2: extensive streamlinin