Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive therapy for partial seizures in patients. Although many neuro-psychiatric and non-cardiac drugs are known to prolong ventricular repolarization as manifested by QTc prolongation on ECG of which provokes torsades de pointes, there is limited data available regarding the characteristics of QT interval in conscious laboratory animals after PRG administration. For that purpose, effects of different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and QTc values in rabbits were evaluated at a predefined time interval in this research. The study involved 28 New Zealand rabbits of both sexes, aged between 8 and 12 months. Animals were divided into four equal groups. Rabbits in control group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, respectively. ECG records were taken before experiment (baseline) and at 1st, 2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph. HR, QT and QTc values were determined from ECG records. Heart rates increased in all groups when compared to baseline values. The increases were evident at 4th h in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III compared with CG. After application of PRG, QTc began to prolong at 1st h through the 4th of experiment and then turned to baseline values at 6th h of the experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and 4th h (p < 0.001) of application in group III were significantly different from CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time and dose dependent (p < 0.001). Increase in HR and QTc prolongation determined in PRG given rabbits may implied that clinicians should take care of these changes when using this drug and further studies are required to fully understand the mechanism involved.
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PMID:Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits. 1872 53

Fibromyalgia (FM) is a common, chronic pain disorder with unknown etiology, characterized by widespread musculoskeletal pain and tenderness, and accompanied by several other symptoms such as sleep disturbance, fatigue, and mood disorders. Pregabalin is the first drug approved for the treatment of FM. Pregabalin has analgesic, anticonvulsant, and anxiolytic activity and has earlier demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy for adult patients with partial onset seizures. Pregabalin, a lipophilic gamma-aminobutyric acid (GABA) analog, is alpha(2)delta-1 ligand that binds to, and modulates, voltage-gated calcium channels. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychotic disorders. Several randomized, double-blind, placebo-controlled studies have demonstrated that pregabalin has been effective in pain management, improving sleep quality and fatigue, as well as in several domains of health related quality of life. Because of mild to moderate adverse effects it can be considered a well-tolerated therapy for FM.
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PMID:New treatment options in the management of fibromyalgia: role of pregabalin. 1933 59

Pregabalin is one of the latest antiepileptic drugs introduced for the treatment of partial epilepsy. Its efficacy and safety as adjunctive therapy in refractory partial epilepsy have been established in four double-blind placebo-controlled trials (n = 1396) and 4 long-term open-label studies (n = 1480). In 3 fixed-dose trials, the proportion of patients with a >/=50% reduction in seizure frequency across the effective dose-range (150-600 mg/day) ranged between 14% and 51%, with a clear dose-response relationship. Suppression of seizure activity could be demonstrated as early as day 2. The most frequently reported CNS-related adverse events included dizziness, somnolence, ataxia and fatigue, were usually mild or moderate, and tended to be dose related. In long-term studies, weight gain was reported as an adverse event by 24% of patients. When pregabalin dose was individualized to according to response within the 150 to 600 mg/day dose range, tolerability was considerably improved compared with use of a high-dose, fixed-dose regimen (600 mg/day) without titration. In long-term studies up to 4 years, no evidence of loss efficacy was identified. During the last year on pregabalin, 3.7% of patients were seizure-free. Pregabalin appears to be a useful addition to the therapeutic armamentariun for the management of refractory partial epilepsy.
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PMID:Pregabalin for the management of partial epilepsy. 1933 61

Pregabalin is a new antiepileptic drug that acts at presynaptic calcium channels, modulating neurotransmitter release. We report on treating consecutive children with severe drug-resistant epilepsy in a prospective, open-label, add-on trial. Nineteen children (63% male) aged 4-15 years (mean, 9.7; S.D., 2.9) were included. Most (74%) had daily seizures that failed multiple drugs (mean, 5). Epilepsy was symptomatic in 58%, and 74% exhibited associated cognitive deficits. Seizures were mixed in nine (47%), and four (21%) manifested Lennox-Gastaut syndrome. Pregabalin was maintained at 150-300 mg/day. On pregabalin, one (6%) child became seizure-free, and seven (37%) had >50% seizure reduction. The percentage of children with daily seizures was reduced from 74% before pregabalin to 37% afterward (P < 0.002). Side effects were evident in six (32%) with somnolence, weight gain, dizziness, or behavioral change. The drug was withdrawn in five (26%) children for lack of efficacy, and in two (11%) for worsening of myoclonic epilepsy. We conclude that pregabalin is a useful addition in the treatment of refractory childhood epilepsy. The drug should be used with caution in myoclonic epilepsy. Controlled studies are needed to establish long-term efficacy and tolerability.
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PMID:Pregabalin: preliminary experience in intractable childhood epilepsy. 1938 70

Pregabalin is a new antiepileptic medication that works by binding to alpha 2 delta subunit of the voltage-dependent calcium channels present in presynaptic neurons. Its pharmacokinetic advantages include rapid and almost complete absorption, lack of protein binding, linear kinetics, absence of enzyme induction, and absence of interactions with other drugs. Pregabalin was found effective as adjunctive therapy for refractory partial-onset seizures, with up to 51% responder at a dose of 600 mg/day. The lowest effective dose was 150 mg/day. Pregabalin is also approved for treatment of painful diabetic polyneuropathy, postherpetic neuralgia and pain with fibromyalgia. Studies also suggest a beneficial effect on sleep and generalized anxiety disorders. Its main adverse effects in randomized adjunctive trials in adults have been mild to moderate. Most common side effects were dizziness, ataxia, somnolence and diplopia. Weight gain was not prominent in pivotal pregabalin trials, but was more problematic in long-term postmarketing analyses in epilepsy patients. Pregabalin, with its potent antiseizure effect, favorable pharmacokinetic profile, and effectiveness in common co-morbidities is an important addition to the treatment of epilepsy.
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PMID:Pregabalin in the management of partial epilepsy. 1972 20

Lacosamide ((R)-2-acetamido-N-benzyl-3-methoxypropionamide; formerly harkoseride, SPM 927; Vimpat), has been recently approved by US and European regulatory authorities for use as add-on therapy for partial-onset seizures in adults. Because a number of anti-epileptic drugs are used to treat conditions beyond epilepsy, including anxiety, in the present study we investigated the anxiolytic potential of lacosamide in a conditioned emotional response (CER) model in rat, and the mouse marble burying assay. In each test lacosamide produced a significant effect consistent with anxiolysis, i.e. lacosamide increased suppression ratio in the CER test, and reduced the number of marbles buried in the marble burying assay. The doses necessary for an anxiolytic effect were higher than those necessary for efficacy in seizure tests conducted in the same species. For example in the mouse, the lacosamide oral ED(50) in the maximal electroshock seizure (MES) and 6 Hz tests was 5.3 and 9.6 mg/kg respectively, and the minimal effective dose in the marble burying assay was 30 mg/kg. In both seizure and anxiety tests, the (S)-enantiomer of lacosamide was inactive suggesting a similar mechanism of action, possibly use-dependent inhibition of sodium channel function (Errington et al., 2008). Efficacy in the CER model was equivalent to diazepam and pregabalin (Lyrica). In tests of side-effects, lacosamide had no effect on choice accuracy in the delayed match to position task of working memory, although at the 30 mg/kg dose, response rates and response latencies were significantly affected. In sum, the present results identify for the first time, an anxiolytic potential of lacosamide.
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PMID:The anti-epileptic drug lacosamide (Vimpat) has anxiolytic property in rodents. 1981 46

Pregabalin has shown clinical efficacy for treatment of neuropathic pain syndromes, partial seizures, and anxiety disorders. Five studies in healthy volunteers are performed to investigate single- and multiple-dose pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral administration, with peak plasma concentrations occurring between 0.7 and 1.3 hours. Pregabalin oral bioavailability is approximately 90% and is independent of dose and frequency of administration. Food reduces the rate of pregabalin absorption, resulting in lower and delayed maximum plasma concentrations, yet the extent of drug absorption is unaffected, suggesting that pregabalin may be administered without regard to meals. Pregabalin elimination half-life is approximately 6 hours and steady state is achieved within 1 to 2 days of repeated administration. Corrected for oral bioavailability, pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable, predictable pharmacokinetic properties that suggest ease of use. Because pregabalin is eliminated renally, renal function affects its pharmacokinetics.
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PMID:Clinical pharmacokinetics of pregabalin in healthy volunteers. 2014 18

Gamma aminobutyric acid (GABA) represents the major inhibitory neurotransmitter of the central nervous system. Ethanol as well as benzodiazepines (BDZs) and some anticonvulsant drugs directly affect GABAA receptors inducing similar anxiolytic, sedativehypnotic, and anticonvulsant effects. Since BDZs have proven their efficacy in ameliorating symptoms and in decreasing the risk of seizures and delirium tremens, they are the drugs of choice for the treatment of alcohol withdrawal syndrome (AWS). However, due to their addictive potential and lack of safety when combined with alcohol, BDZs are usually not recommended for the maintenance of alcohol abstinence. Other GABA-ergic medications represent potentially promising drugs useful in the treatment of AWS and in maintaining alcohol abstinence. Indeed, available studies have demonstrated that clomethiazole, gabapentin and gamma hydroxybutyrate (GHB) present a similar efficacy to BDZs in suppressing AWS. In addition, current evidence also indicates that gabapentin and GHB do not have significant interactions with ethanol that render them safe to use in maintaining alcohol abstinence. Moreover, gabapentin and valproic acid may be beneficial in maintaining alcohol abstinence in alcoholics with psychiatric co-morbidity. Pregabalin, neurosteroids, tiagabine, and vigabatrin need further clinical evidence of efficacy, safety and tolerability. Thus, given the importance of GABA-ergic mechanisms in the development and maintenance of alcohol dependence, and the very interesting results currently achieved, more research on GABAergic agents is warranted.
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PMID:Medications acting on the GABA system in the treatment of alcoholic patients. 2048 12

The management of epilepsy and neuropathic pain poses a substantial burden on individuals and society with significant healthcare resource implications. Pregabalin has been approved for add-on treatment of adults with partial seizures with or without secondary generalization and for central and peripheral neuropathic pain syndromes. New antiepileptic drugs, such as pregabalin, have higher acquisition costs than established 'off-patent' drugs, but boast advantages in terms of efficacy, tolerability and side-effect profiles. There is, however, scant health economic research concerning the use of any current antiepileptic drugs used to treat epilepsy and neuropathic pain. This article reviews the available data on pregabalin. There are currently insufficient data to draw conclusions on cost-effectiveness regarding its use in epilepsy, neuropathic pain or other nonepileptic conditions. Long-term retention studies and prescribing practices may give an indication as to the effectiveness and tolerability of pregabalin and consequent cost-effectiveness analyses may then prove useful.
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PMID:Cost-effectiveness of pregabalin: a UK perspective. 2052 14

Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium influx and subsequent release of excitatory neurotransmitters; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours. Orally administered gabapentin exhibits saturable absorption--a nonlinear (zero-order) process--making its pharmacokinetics less predictable. Plasma concentrations of gabapentin do not increase proportionally with increasing dose. In contrast, orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour. Absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage. Both drugs can be given without regard to meals. Neither drug binds to plasma proteins. Neither drug is metabolized by nor inhibits hepatic enzymes that are responsible for the metabolism of other drugs. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours. Pregabalin and gabapentin both show dose-response relationships in the treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a pregabalin dosage of 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be more effective than gabapentin, on the basis of the magnitude of the reduction in the seizure frequency. In conclusion, pregabalin appears to have some distinct pharmacokinetic advantages over gabapentin that may translate into an improved pharmacodynamic effect.
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PMID:A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. 2081 32


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