1,720,993 research outputs found
Progress report on new antiepileptic drugs: a summary of the Fourth Eilat Conference
No full textThe Fourth Eilat Conference on New Antiepileptic Drugs (AEDs) was held at the Royal Beach Hotel, Eilat, Israel, from 6th to 10th September 1998. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss a number of issues in drug development, including outcome assessment in epilepsy (long-term efficacy, quality of life, safety), cost-effectiveness, an update on drugs in development, a progress report on recently marketed AEDs, and controversies in strategies for drug development. This review focuses on drugs in development and recently marketed AEDs. Drugs in development include ADCI, AWD 131-138, DP16, ganaxolone (CCD 1042), levetiracetam (ucb L059), losigamone, pregabalin (isobutyl GABA [CI-1008]), remacemide hydrochloride, retigabine (D-23129), rufinamide (CGP 33101), soretolide (D2916), TV1901, and 534U87. New information on the safety and efficacy of recently marketed drugs (felbamate, fosphenytoin, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide) and of a new antiepileptic device, the neurocybernetic prosthesis (NCP), has become available. This paper summarizes the presentations made at the conference
Predictability of metabolic antiepileptic drug interactions
No full textMany drugs are lipid soluble, weak organic acids or bases that are not readily eliminated from the body, being reabsorbed into the blood from the glomerular filtrate. Metabolic processes are necessary to convert a drug into one or more metabolites which are chemically different from the parent compound, but generally more polar and water soluble, facilitating their excretion in urine or bile. Although metabolism usually results in inactivation or detoxification, many drug metabolites have pharmacological activity. Metabolites may occasionally be much more active than the parent compound (which then may be designated as a prodrug), they may exert effects similar to or different from those of the parent molecule, or they may be responsible for toxic effects (Perucca and Richens, 1995). When metabolites are active, termination of their action occurs by further biotransformation or by direct excretion of the metabolite in urine or bile.
The chemical reactions involved in the biotransformation of drugs are catalyzed by various enzyme systems and are conventionally divided into phase I (functionalization) and phase II (conjugation) biotransformation reactions, which may occur in series. Phase I reactions involve the addition of a polar functional group (e.g. a hydroxyl group) or the deletion of a non-polar alkyl group (e.g. N-demethylation) by oxidation, reduction, or hydrolysis
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).
No full textThe Fifth Eilat Conference on New Antiepileptic Drugs (AEDs) took place at the Dan Hotel, Eilat, Israel, 25-29 June 2000. Basic scientists, clinical pharmacologists and neurologists from 20 countries attended the conference, whose main themes included recognition of unexpected adverse effects, new indications of AEDs, and patient-tailored AED therapy. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs that have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including AWD 131-138, DP-valproate, harkoseride, LY300164, NPS 1776, NW 1015, pregabalin, remacemide, retigabine, rufinamide and valrocemide. The potential value of an innovative strategy, porcine embryonic GABAergic cell transplants, is also discussed. Finally, updates on felbamate, fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, and the antiepileptic vagal stimulator device are presented
Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX).
No full textThe Ninth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT IX, took place in Sitges, Barcelona from the 15th to 19th of June 2008. Over 300 basic scientists, clinical pharmacologists and neurologists from 25 countries attended the conference, whose main themes included old and new AEDs in generalized epilepsies, novel formulations and routes of administration of AEDs, common targets and mechanisms of action of drugs for treating epilepsy and other central nervous system (CNS) disorders, and opportunities and perspectives in new AED discovery. Consistent with previous formats of this conference, a large part of the programme was devoted to a review of AEDs in development, as well as updates on AEDs introduced since 1989. Unlike previous EILAT manuscripts, the current (EILAT IX) manuscript focuses only on the preclinical and clinical pharmacology of AEDs that are currently in development. These include brivaracetam, carisbamate (RWJ-333369), 2-deoxy-d-glucose, eslicarbazepine acetate (BIA-2-093), ganaxolone, huperzine, JZP-4, lacosamide, NAX-5055, propylisopropylacetamide (PID), retigabine, T-2000, tonabersat, valrocemide and YKP-3089. The CNS efficacy of these compounds in anticonvulsant animal models as well as other disease model systems are presented in first and second tables and their proposed mechanisms of action are summarized in the third table
The amplitude and origin of sea-level variability during the Pliocene epoch
No full textEarth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'(1), when atmospheric carbon dioxide concentrations were about 400 parts per million, global sea level oscillated in response to orbital forcing(2,3) and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value(4,5). For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 +/- 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy(3) (as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession(6) between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere(3,6). Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century
Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI).
No full textThe Sixth Eilat Conference on New Antiepileptic Drugs (AEDs) took place in Taormina, Sicily, Italy from 7th to 11th April, 2002. Basic scientists, clinical pharmacologists and neurologists from 27 countries attended the conference, whose main themes included dose-response relationships with conventional and recent AEDs, teratogenic effects of conventional and recent AEDs, update on clinical implications of AED metabolism, prevention of epileptogesis, and seizure aggravation by AEDs. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs, which have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including carabersat (SB-204269), CGX-1007 (Conantokin-G), pregabalin, retigabine (D-23129), safinamide, SPD421 (DP-VPA), SPM 927, talampanel and valrocemide (TV 1901). Updates on fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, new formulations of valproic acid, and the antiepileptic vagal stimulator device are also presented
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
