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 is a novel anticonvulsive and analgesic drug that has been marketed in Europe for more than a year. The typical side effects are dizziness, somnolence and weight gain. We present a patient who, after unintended rapid up-titration of pregabalin, experienced psychotic symptoms associated with rhythmic EEG-changes resolving completely after discontinuation of pregabalin and benzodiazepine administration.
Seizure 2006 Apr
PMID:Pregabalin-associated acute psychosis and epileptiform EEG-changes. 1653 Apr 31

Pregabalin, ((S)-3-(aminomethyl)-5-methylhexanoic acid, also known as (S)-3-isobutyl GABA, Lyricatrade mark) is approved for treatment of certain types of peripheral neuropathic pain and as an adjunctive therapy for partial seizures of epilepsy both the EU and the USA and also for generalized anxiety disorder in the EU. Though pregabalin binds selectively to the alpha(2)-delta (alpha(2)-delta) auxiliary subunit of voltage-gated calcium channels, the cellular details of pregabalin action are unclear. The high density of alpha(2)-delta in skeletal muscle fibers raises the question of whether pregabalin alters excitation-contraction coupling. We used the mouse soleus neuromuscular junction from mice containing an artificially mutated alpha(2)-delta Type 1 protein (R217A) as a model to examine the effect of pregabalin. Pregabalin reduced nerve-evoked muscle contractions by 16% at a clinically relevant concentration of 10 muM in wildtype mice. When acetylcholine receptors were blocked with curare, pregabalin had no effect on contraction from direct stimulation of muscle, suggesting a lack of drug effects on contraction coupling. Our data are consistent with pregabalin having no effect on striated muscle L-type calcium channel function. However, in mice expressing mutant (R217A) alpha(2)-delta Type 1, there was no significant effect of pregabalin on nerve-evoked muscle contraction. We propose that pregabalin reduces presynaptic neurotransmitter release without altering postsynaptic receptors or contraction coupling and that these effects require high affinity binding to alpha(2)-delta Type 1 auxiliary subunit of presynaptic voltage-gated calcium channels.
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PMID:Pregabalin action at a model synapse: binding to presynaptic calcium channel alpha2-delta subunit reduces neurotransmission in mice. 1706 82

Pregabalin (Lyrica) is a new antiepileptic drug that is active in animal seizure models. Pregabalin is approved in US and Europe for adjunctive therapy of partial seizures in adults, and also has been approved for the treatment of pain from diabetic neuropathy or post-herpetic neuralgia in adults. Recently, it has been approved for treatment of anxiety disorders in Europe. Pregabalin is structurally related to the antiepileptic drug gabapentin and the site of action of both drugs is similar, the alpha2-delta (alpha2-delta) protein, an auxiliary subunit of voltage-gated calcium channels. Pregabalin subtly reduces the synaptic release of several neurotransmitters, apparently by binding to alpha2-delta subunits, and possibly accounting for its actions in vivo to reduce neuronal excitability and seizures. Several studies indicate that the pharmacology of pregabalin requires binding to alpha2-delta subunits, including structure-activity analyses of compounds binding to alpha2-delta subunits and pharmacology in mice deficient in binding at the alpha2-delta Type 1 protein. The preclinical findings to date are consistent with a mechanism that may entail reduction of abnormal neuronal excitability through reduced neurotransmitter release. This review addresses the preclinical pharmacology of pregabalin, and also the biology of the high affinity binding site, and presumed site of action.
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PMID:Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. 1712 31

Pregabalin is similar in structure to gamma-aminobutyric acid. It is used for neuropathic pain, generalized anxiety disorders and as an adjunct therapy for partial seizures. Tachycardia is a rare side-effect. A 92-year-old patient with a history of paroxystic fibrillation was hospitalised for zoster. She developed a sinusal tachycardia followed by atrial fibrillation and congestive heart failure 15 h after a first dose of pregabalin. The imputation was considered as plausible. Even though the mechanism remains unclear, pregabalin might induce tachycardia in predisposed old patients.
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PMID:[Should we care about pregabalin for elderly patients with a history of cardiac dysrhythmia?]. 1797 66

Pregabalin (PGB) is a new antiepileptic drug (AED) approved for adjunctive therapy for partial seizures with and without generalized tonic-clonic seizures and for the treatment of peripheral neuropathic pain in adults. PGB does not bind to plasma proteins and is excreted predominantly unchanged by the kidneys. Previous studies indicated that PGB shows no relevant interactions with other AEDs. The aim of this study was to investigate the influence of PGB dose, patient age, and comedication on the serum concentration of PGB. In total, 198 samples of 167 (adult) inpatients who fulfilled the inclusion criteria (eg, trough concentration, body weight available) were investigated. A patient was considered twice only if the comedication had been changed. The PGB serum concentration (mg/L) in relation to PGB dose/body weight (mg/kg) per day (level-to-dose ratio, LDR, [(mg/L)/(mg/kg)=kg/L]) was calculated and compared for the most frequent drug combinations (n=97). Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that comedication had a slight but significant (P = 0.02) effect on PGB serum concentrations. The median LDR of PGB was 0.29 for PGB + oxcarbazepine (n=16), 0.31 for PGB + carbamazepine (n=20), 0.35 for PGB + levetiracetam (n=11), 0.35 for PGB + lamotrigine (n=15), and 0.39 for PGB + valproic acid + lamotrigine (n=35). Regression analysis including all 198 samples indicated (in accordance with analysis of covariance) that PGB concentrations were lower in combination with enzyme-inducing AEDs (phenytoin, carbamazepine, oxcarbazepine) and were age-dependent (higher in older patients). The PGB dose-concentration relationship was nearly linear (r=0.68, P<0.0001). However, patients on the same PGB dosage per body weight had rather different PGB trough concentrations, which could be explained only in part by age and comedication. The increase of PGB serum concentrations in older patients is in accordance with expectations for drugs that are predominantly renally excreted. Unexpectedly and in contrast to other studies, our data indicate that comedication with enzyme-inducing antiepileptic drugs (eg, carbamazepine) can moderately decrease PGB serum concentrations (about 20% to 30%). Further studies should clarify the effect of age and interactions on PGB concentrations.
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PMID:Serum concentrations of pregabalin in patients with epilepsy: the influence of dose, age, and comedication. 1804 77

Synthesized in 1990 as an anticonvulsant agent, pregabalin was designed as a lipophilic gamma-aminobutyric acid (GABA) analog substituted at the 3'-position in order to facilitate diffusion across the blood-brain barrier. It is an alpha2delta1 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 neurologic and psychotic disorders. Pregabalin has analgetic, anticonvulsant, and anxiolytic activity and has 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 was significantly more effective than placebo for the treatment of generalized anxiety disorder as well as of fibromyalgia and was well tolerated by most of the patients.
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PMID:[Pregabalin--a neuromodulator for the treatment of neuropathic pain, generalized anxiety disorders and fibromyalgia syndrome]. 1806 30

Myoclonus is a well-known side effect of anticonvulsant drugs. Pregabalin is one of the newer drugs approved for the treatment of focal epilepsies. Frequently it is also used to treat chronic pain syndromes. We describe a patient who, after receiving his first dose of pregabalin to relieve neuropathic pain, presented with a negative myoclonus. Clinical aspects and electrophysiological data such as polygraphic studies, electroencephalography, and measurement of somatosensory evoked potentials support the cortical origin of negative myoclonus. Our findings reveal that even in patients without a history of seizures, pregabalin can cause a cortical negative myoclonus.
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PMID:Pregabalin-induced cortical negative myoclonus in a patient with neuropathic pain. 1849 17

Epilepsy is common in the pediatric population. Nine second-generation antiepileptic drugs have been approved in the US for use in epilepsy over the past 15 years: felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, zonisamide, and pregabalin. Their use in pediatric patients is fairly widespread, despite most of these agents not having US FDA indications for use. Felbamate and gabapentin were the first two second-generation antiepileptic drugs to be approved in the US. Felbamate use has been limited because of the occurrence of hepatotoxicity and aplastic anemia. Although gabapentin is a fairly well tolerated antiepileptic drug, its use has also been limited as a result of inconsistent efficacy and concern about seizure exacerbation. Lamotrigine and topiramate are broad-spectrum antiepileptic drugs with efficacy in a wide variety of seizure types. Both agents have some tolerability concerns: rash with lamotrigine and neuropsychiatric events with topiramate. There are very little data on tiagabine use in children, but this agent appears to be effective and to have a good tolerability profile. Levetiracetam is a second-generation antiepileptic agent that is available intravenously. Considering its good efficacy, fast onset of action, and low incidence of serious adverse effects, its use in the acute setting could potentially increase. Oxcarbazepine and zonisamide have been relatively well studied in pediatric seizure patients, including use as monotherapy. Both agents have demonstrated good efficacy and tolerability for patients as young as 1 month old. Vigabatrin and rufinamide are currently not available in the US, but have been shown to have some success in other countries. Pregabalin is the newest antiepileptic agent, but lacks pediatric data currently.
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PMID:Use of second-generation antiepileptic drugs in the pediatric population. 1859 Mar 43

Pregabalin, the most recently approved antiepileptic drug, is a structural analog of GABA with a favorable pharmacokinetic profile. Pregabalin binds to the alpha2-delta subunit of a neuronal voltage-gated calcium channel and is believed to exert its anticonvulsant effect by modulating the release of specific neurotransmitters from hyperexcited presynaptic neurons. Animal models of epilepsy have suggested that this drug will be efficacious against partial-onset and generalized tonic-clonic seizures. Four pivotal, add-on clinical trials conducted in patients with partial-onset seizures demonstrated that pregabalin at daily doses of 150-600 mg is efficacious and associated with dose-dependent adverse events. Meta-analyses of efficacy and tolerability indicated that pregabalin is an efficacious and relatively well-tolerated antiepileptic drug.
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PMID:Efficacy and tolerability of pregabalin in partial epilepsy. 1859 Apr 72

Antiepileptic drugs (AED) are increasingly used in the treatment of migraine. Pregabalin (PGB) is an AED that has been used in the treatment of partial seizures, of various types of pain, and of certain anxiety disorders, but to the best of our knowledge, there has been no report on the use of PGB in the treatment of migraine. We report the case of a 60-year-old female inpatient with depression, long experiencing migraine, whose migraine symptoms improved markedly after receiving PGB in combination with escitalopram administered for her depression. The PGB mechanism of action in conjunction with its structural similarity with gabapentin, already successfully tested in the treatment of migraine, provide additional supportive evidence, theoretical and clinical, respectively, for PGB potential to alleviate migraine symptoms. However, only carefully randomized, controlled studies, or at the very least, open-label series of large patient samples treated in a similar fashion could establish the efficacy of PGB in migraine treatment.
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PMID:Remission of migraine attacks in a patient with depression who is taking pregabalin. 1867 Feb 48


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