An electrospray ionization-flow tube study of H/D exchange in protonated bradykinin

An electrospray ionization-fast flow technique has. been employed to study the reactions of doubly protonated bradykinin and des-Arg(9)-bradykinin with CH3OD and ND3, respectively. Deconvolution of the experimental mass spectral data followed by simulation of the kinetic data by solution of differential equations leads to sets of apparent and site specific rate constants. On a time scale of several milliseconds, bradykinin undergoes with ND3 three fast HID exchanges and one slow exchange. Three equivalent exchanges are observed with CH3OD that are nearly 2 orders of magnitude slower than the ND3 reactions. Up to six hydrogen exchanges are observed for the reaction of des-Arg(9)-bradykinin with ND3. The more efficient exchange of des-Arg(9)- bradykinin is accompanied by formation of collisionally stabilized complexes between doubly protonated des-Arg(9)-bradykinin and ND3 at a He carrier gas pressure of about 0.2 Torr. Multiple-collision activation-collision-induced dissociation of reactant and product ions of the isotope exchange reactions was carried out in front of the sampling nose cone of the analyzer quadrupole mass filter system. The degree of deuterium incorporation into the parent doubly protonated ions and into several of the b(n)(+) and y(n)(+) ions combined with the site-specific rate constants obtained indicates that the three equivalent hydrogens exchanged in doubly protonated bradykinin are at the protonated N-terminus amine group. Complexation of doubly protonated bradykinin by ND3 is prevented by its tightly folded structure, and this in turn prevents H/D exchange of the amide hydrogens of bradykinin. The additional H/D exchanges observed in the case of doubly protonated des-Arg(9)-bradykinin are made possible by complexation of its less compact structure via hydrogen-bonded intermediates that promote H/D exchange of amide hydrogens

Zonisamide as a Treatment for Partial Epileptic Seizures: A Systematic Review

Although the majority of people with epilepsy have a good prognosis and their seizures can be well controlled with pharmacotherapy, up to one-third of patients can develop drug-resistant epilepsy, especially those patients with partial seizures. This unmet need has driven considerable efforts over the last few decades aimed at developing and testing newer antiepileptic agents to improve seizure control. One of the most promising antiepileptic drugs of the new generation is zonisamide, a benzisoxazole derivative chemically unrelated to other anticonvulsant agents. In this article, the authors present the results of a systematic literature review summarizing the current evidence on the efficacy and tolerability of zonisamide for the treatment of partial seizures. Of particular interest within this updated review are the recent data on the use of zonisamide as monotherapy, as they might open new therapeutic avenues. </p