bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixing Sumatriptan: A Prospective Study of Stratified Care Using Multiple Formulations
Authors: Kaniecki Robert G. 
Published: August 2010

Objective.—To assess the acceptability, utility, and tolerability of a system of stratified care of acute migraine using multiple formulations of sumatriptan.Background.—Stratified care matches the treatment of a disease to its level of severity. Sumatriptan, with its multiple formulations, seems a logical option in a stratified care approach. Little data exists on the use of multiple formulations in a single patient population.Design and Methods.—A prospective, open‐label, outpatient study recruited patients from a single center during the period from January 1998 through June 1998. Entry criteria included International Headache Society migraine diagnostic codes 1.1 or 1.2 and an established response to sumatriptan tablets or nasal spray. Patients who enrolled were allowed to use subcutaneous sumatriptan as either primary or rescue therapy for individual migraine attacks.Results.—Two hundred eighteen (80%) of 273 patients on tablets and 40 (85%) of 47 patients on nasal spray enrolled. During a period of 6 months, 61% of the patients on tablets and 85% of the patients using the nasal spray used at least one subcutaneous dose of sumatriptan. This system was efficacious and well tolerated. The majority of injections were used as rescue treatments following a failed oral or nasal dose. Two percent withdrew due to lack of efficacy, and 6% withdrew due to adverse events; however, 92% professed satisfaction with subcutaneous sumatriptan as an available tool for migraine management.Conclusion.—A system of stratified care using multiple formulations of sumatriptan is efficacious, well tolerated, and preferable to a program involving a single form of the drug.
Topiramate for Migraine Prevention in Children: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Winner Paul , Pearlman Eric M. , Linder Stephen L. , Jordan Donna M. , Fisher Alan C. , Hulihan Joseph ,   for the Topiramate Pediatric Migraine Study Investigators
Published: August 2010

Objective.—To assess the efficacy and safety of topiramate for the prevention of pediatric migraine with or without aura in a double‐blind, randomized, placebo‐controlled trial.Background.—Treatment options for pediatric migraine are currently limited, and no migraine preventive agents are approved for use in children in the United States. Topiramate is an effective migraine preventive therapy in adults, as demonstrated in several large, randomized, placebo‐controlled trials.Methods.—One hundred and sixty‐two children with migraine (age, 6 to 15 years) were randomized in a 2:1 ratio to receive topiramate (n = 112) or placebo (n = 50). This study was designed to ensure that 150 participants were randomized to study medication. An additional 12 qualified patients were randomized because they had successfully completed the screening phase. The double‐blind phase of the trial consisted of a titration period and a maintenance period. Topiramate was initiated at 15 mg/day and titrated over 8 weeks to 2 to 3 mg/kg per day, or maximum tolerated dose, whichever was less (maximum allowed dose was 200 mg/day). The target dose was maintained for 12 weeks. The primary efficacy variable was the change in mean number of migraine days per month (28 days) during the double‐blind phase relative to the 4‐week prospective baseline phase for each treatment group.Results.—Topiramate treatment was associated with a mean reduction over the entire double‐blind phase of 2.6 migraine days per month, compared with a mean reduction of 2.0 migraine days per month for placebo (P= .061 topiramate vs. placebo). A significantly greater percentage of topiramate patients (32%) experienced a ≥75% reduction in mean monthly migraine days compared with placebo (14%, P= .02). Discontinuation rates due to adverse events were low: 6.5% for the topiramate group and 4.0% for the placebo group. The adverse events that occurred most commonly in the topiramate group at an incidence rate greater than in the placebo group were: upper respiratory tract infection, anorexia, weight decrease, gastroenteritis, paresthesia, and somnolence. The mean average daily dose of topiramate during the maintenance period was 2.0 mg/kg per day.Conclusions.—This pilot study suggests that topiramate may be an effective migraine preventive therapy in children. Topiramate was well tolerated in this population. Further randomized studies would be required to definitively establish the efficacy of topiramate for pediatric migraine prevention.
Visual Cortex Excitability in Migraine Evaluated by Single and Paired Magnetic Stimuli
Authors: Gerwig Marcus , Niehaus Ludwig , Kastrup Oliver , Stude Philipp , Diener Hans C. 
Published: August 2010

Objective.—To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single‐ and paired‐pulses.Methods.—Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti‐migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single‐pulse and paired‐pulse TMS with an interstimulus interval of 50 ms.Results.—The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P= .001). Using single‐pulse TMS, mean PT tended to be lower in MWoA‐patients (57.7 ± 11.8%) compared with control subjects (64.4 ± 10.5%) (P= .064). In MWA‐patients, mean PT (53.1 ± 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA‐patients (40.3 ± 4.9%, P= .017) as well as in MWA‐patients (39.6 ± 4.2%, P= .005) compared with controls (44.6 ± 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired‐pulse stimulation than with single pulses (P < .001).Conclusions.—PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single‐pulse TMS, paired‐pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.
Visual Stimuli Are Common Triggers of Migraine and Are Associated With Pattern Glare
Authors: Harle Deacon E. , Shepherd Alex J. , Evans Bruce J.W. 
Published: August 2010

Objective.—To investigate the associations between interictal pattern glare, visual stress, and visual triggers of migraine.Background.—There has been relatively little research on the visual stimuli that can trigger migraine episodes. This is surprising, since if practitioners can obviate such triggers, then some attacks may be prevented. The existing literature suggests that patients who are prone to visually triggered migraines report more illusions on viewing striped patterns (“pattern glare”) and that colored filters may be an effective intervention for these people.Methods.—Headache symptoms and headache triggers were investigated in migraine and control groups in 2 separate experiments. In one experiment, we also determined, for each participant, pattern glare, whether it was reduced by colored filters and, if so, what the optimum color of filter was. Color vision was also assessed with the D15 test.Results.—People with migraine saw significantly more illusions on viewing each striped pattern and experienced greater pattern glare. They were also more likely to select a colored filter to aid visual comfort, particularly colors in the blue‐to‐green sector of the spectrum. Color vision was impaired subtly but significantly in migraine. Principal component analyses grouped common headache triggers into 5 broadly equal components: food, visual triggers, alcohol, stress and tiredness, and the environment. In a second analysis, the overall number of illusions seen in striped patterns was associated with visual triggers while pattern glare, use of colored filters, and interictal light sensitivity together formed a sixth component interpreted as visual stress.Conclusions.—It is suggested that clinicians should ask migraine patients whether visual stimuli trigger their migraine, about interictal visual symptoms, and use the pattern glare test to ensure that those who may benefit from optometric interventions are appropriately managed.
Insulin Metabolism is Altered in Migraineurs: A New Pathogenic Mechanism for Migraine?
Authors: Cavestro Cinzia , Rosatello Annalisa , Micca GianMatteo , Ravotto Marisa , Pia Marino Maria , Asteggiano Giovanni , Beghi Ettore 
Published: August 2010

Background.— Migraine is a complex biochemical dysfunction attributed to a disorder of the trigeminal and hypothalamic pathways. Impairment of glucose metabolism has been reported in migraine, but data are scanty and inconsistent.Objective.— The main aim was to verify whether migraineurs have abnormalities of the glucose and insulin metabolism.We also studied correlations between blood glucose and insulin and between insulin levels and migraine severity.Patients and methods.— Patients with migraine or headache other than migraine, and healthy volunteers were included. All had general blood tests and a standard oral glucose tolerance test after a 12‐hour fast, and glucose and insulin were measured.Results.— Over a 6‐month period, we recruited 84 migraineurs (73 women, 11 men), 25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls (24 women, 2 men). Multivariate analysis confirmed a significant difference between groups for glucose levels (P < .0001), but no significant time interaction. The differences were mostly between migraine and healthy controls (P < .0001) and to a lesser extent between other headaches and healthy controls (P < .05). A significant difference between groups was also found for insulin (P < .0001), with a significant time interaction. The difference was confirmed for migraine compared to other headaches (P < .0001) and healthy controls (P < .0001).Conclusions.— Blood glucose levels may be high in headache patients, but do not seem to be specific to migraineurs. Insulin levels were higher in migraineurs, and seemed specific to this group. These findings are in keeping with recent reports on the effects of insulin on brain functions and lend support to the possibility that insulin is involved in the pathogenesis of migraine.
Levetiracetam Prophylaxis in Pediatric Migraine—An Open‐Label Study
Authors: Pakalnis Ann , Kring Donna , Meier Lisa 
Published: August 2010

Background.—Migraine is common in the pediatric population. Levetiracetam, an anti‐epileptic drug, has shown some efficacy in small prospective adult headache studies.Methods.—We prospectively evaluated levetiracetam in an open‐label study in 20 pediatric migraine patients to assess tolerability and efficacy.Results.—Eighteen of 20 patients had significant reduction in headache frequency. PedMIDAS showed significant decrease in disability scores, side effects were minimal (mild behavioral changes).Conclusion.—Levetiracetam had some efficacy in reducing migraine frequency and disability. Further larger studies are warranted, possibly utilizing a placebo‐controlled design.
Eletriptan for the Acute Treatment of Migraine in Adolescents: Results of a Double‐Blind, Placebo‐Controlled Trial
Authors: Winner Paul , Linder Steven L. , Lipton Richard B. , Almas Mary , Parsons Bruce , Pitman Verne 
Published: August 2010

Background.—Eletriptan is a potent 5‐HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults.Objective.—To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12‐17).Methods.—A multicenter, double‐blind, parallel‐group, placebo‐controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2‐hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response.Results.—Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post‐dose. There was no significant difference in 2‐hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post‐dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post‐dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain‐free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan‐naïve status (ie, no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients.Conclusions.—The high placebo response rates reported here for 1‐ and 2‐hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain‐free response at 24 hours post‐dose.
Ibogaine and Noribogaine: Comparing Parent Compound to Metabolite
Authors: Zubaran Carlos 
Published: August 2010

ABSTRACTIbogaine is one of the psychoactive alkaloids found in the West African shrubTabernanthe iboga.Since the 1980s, a series of US patents have claimed efficacy for ibogaine in the treatment of drug addiction. Since then, more than 60 scientific publications on ibogaine and drug addiction have been published. Ibogaine has an acute and a prolonged effect on neurochemistry and behavior. Its metabolite, noribogaine (12‐hydroxyibogamine), is produced through metabolic demethylation soon after oral ibogaine administration. Although, they share similar chemical structures, ibogaine and noribogaine display different binding profiles. In rodents both, ibogaine and noribogaine, decreased morphine and cocaine intake and modulated dopaminergic transmission. In rats trained to discriminate ibogaine from saline, complete generalization to noribogaine was obtained. Attempts to correlate brain levels of both, the parent compound and the metabolite indicate that noribogaine is primarily responsible for ibogaine discriminative stimulus. Ibogaine‐induced neurotoxicity tends to occur at doses much higher than the proposed dose for humans, but caution is important when extrapolating data from ibogaine's effects observed in rodents. Although a definitive clinical validation of purported ibogaine effects is still unavailable, ibogaine has opened new perspectives in the investigation of pharmacotherapies for drug addiction.
RX 821002 as a Tool for Physiological Investigation of α2‐Adrenoceptors
Authors: Clarke R. W. , Harris J. 
Published: August 2010

ABSTRACTRX 821002 is the 2‐methoxy congener of idazoxan. In binding and tissue studies it behaves as a selective antagonist of α2‐adrenoceptors, with at least 5 times greater affinity for these receptors than any other binding site. It does not select between the different types of α2‐receptor. Although this drug probably has no future as a therapeutic agent, it remains a good probe for physiological activity at α2‐adrenoceptors in animal experiments. A particularly useful feature of this compound is its lack of binding at I1and I2imidazoline receptors. However, it has relatively high affinity for 5‐HT1Areceptors (at which it acts as an antagonist) and a tendency to behave as an inverse agonist at α2A‐adrenoceptors in some cell culture systems. These potential drawbacks may be overcome by careful design of experiments, and the greater selectivity of RX 821002 renders it much superior to yohimbine or idazoxan as a tool for probing physiological actions at α2‐receptors. It can be compared favorably with other selective antagonists such as atipamezole.In physiological studies, RX 821002 augments norepinephrine release in the frontal cortex and increases drinking behavior in rat. In rabbit, intrathecal administration of this drug enhances somatic and autonomic motor outflows, showing that tonic adrenergic descending inhibition of withdrawal reflexes and sympathetic pre‐ganglionic neurons is strong in this species. The potentiation of reflexes may be considered a pro‐nociceptive action. In the same model, RX 821002 antagonizes the inhibitory effects of the μ opioid fentanyl, indicating that exogenous opioids synergize with endogenously released norepinephrine in the spinal cord. Thus, the careful use of RX 821002 has revealed several aspects of the physiological activity of α2‐adrenoceptors in rabbit spinal cord and rat brain. We recommend that RX 821002 and/or compounds with similar selectivity for α2‐adrenoceptors (atipamezole, MK‐912, RS‐79948) should be used in preference to yohimbine or idazoxan in all future studies of this type.
LY404187: A Novel Positive Allosteric Modulator of AMPA Receptors
Authors: Quirk Jennifer C. , Nisenbaum Eric S. 
Published: August 2010

ABSTRACTLY404187 is a selective, potent and centrally active positive allosteric modulator of AMPA receptors. LY404187 preferentially acts at recombinant human homomeric GluR2 and GluR4 versus GluR1 and GluR3 AMPA receptors. In addition, LY404187 potentiates the flip splice variant of these AMPA receptors to a greater degree than the flop splice variant. In both recombinant and native AMPA receptors, potentiation by LY404187 displays a unique time‐dependent growth that appears to involve a suppression of the desensitization process of these ion channels. LY404187 has been shown to enhance glutamatergic synaptic transmission bothin vitroandin vivo.This augmentation of synaptic activity is due to the direct potentiation of AMPA receptor function, as well as an indirect recruitment of voltage‐dependent NMDA receptor activity. Enhanced calcium influx through NMDA receptors is known to be a critical step in initiating long‐term modifications in synaptic function (e.g., long‐term potentiation, LTP). These modifications in synaptic function may be substrates for certain forms of memory encoding. Consistent with a recruitment of NMDA receptor activity, LY404187 has been shown to enhance performance in animal models of cognitive function requiring different mnemonic processes. These data suggest that AMPA receptor potentiators may be therapeutically beneficial for treating cognitive deficits in a variety of disorders, particularly those that are associated with reduced glutamatergic signaling such as schizophrenia. In addition, LY404187 has been demonstrated to be efficacious in animal models of behavioral despair that possess considerable predictive validity for antidepressant activity. Although the therapeutic efficacy of AMPA receptor potentiators in these and other diseases will ultimately be determined in the clinic, evidence suggests that the benefit of these compounds will be mediated by multiple mechanisms of action. These mechanisms include direct enhancement of AMPA receptor function, secondary mobilization of intracellular signaling cascades, and prolonged modulation of gene expression.
Dehydroepiandrosterone (DHEA) and the Aging Brain: Flipping a Coin in the “Fountain of Youth”
Authors: Racchi Marco , Balduzzi Carla , Corsini Emanuela 
Published: August 2010

ABSTRACTThe physiological role of dehydroepiandrosterone (DHEA) and its sulphated ester DHEA(S) has been studied for nearly 2 decades and still eludes final clarification. The major interest in DHEA derives from its unique pattern of activity. Its levels exhibit a dramatic age‐related decline that supports significant involvement of DHEA(S) in the aging process. Particularly relevant to the aging process is the functional decline that involves memory and cognitive abilities. DHEA is derived mainly from synthesis in the adrenal glands and gonads. It can also be detected in the brain where it is derived from a synthesis that is independent from peripheral steroid sources. For this reason DHEA and other steroid molecules have been named “neurosteroids.” Pharmacological studies on animals provided evidence that neurosteroids could be involved in learning and memory processes because they can display memory‐enhancing properties in aged rodents. However, human studies have reported contradictory results that so far do not directly support the use of DHEA in aging‐related conditions. As such, it is important to remember that plasma levels of DHEA(S) may not reflect levels in the central nervous system (CNS), due to intrinsic ability of the brain to produce neurosteroids. Thus, the importance of neurosteroids in the memory process and in age‐related cognitive impairment should not be dismissed. Furthermore, the fact that the compound is sold in most countries as a health food supplement is hampering the rigorous scientific evaluation of its potential. We will describe the effect of neurosteroids, in particular DHEA, on neurochemical mechanism involved in memory and learning. We will focus on a novel effect on a signal transduction mechanism involving a classical “cognitive kinase” such as protein kinase C. The final objective is to provide additional tools to understand the physiological role and therapeutic potentials of neurosteroids in normal and/or pathological aging, such as Alzheimer's disease.
Piracetam: A Review of Pharmacological Properties and Clinical Uses
Authors: Winblad Bengt 
Published: August 2010

ABSTRACTPiracetam, a derivative of the neurotransmitter γ‐aminobutyric acid (GABA), has a variety of physiological effects that may result, at least in part, from the restoration of cell membrane fluidity. At a neuronal level, piracetam modulates neurotransmission in a range of transmitter systems (including cholinergic and glutamatergic), has neuroprotective and anticonvulsant properties, and improves neuroplasticity. At a vascular level, it appears to reduce erythrocyte adhesion to vascular endothelium, hinder vasospasm, and facilitate microcirculation. This diverse range of physiological effects is consistent with its use in a range of clinical indications. Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated.