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PubMed1998

New drugs for persons with epilepsy.

Between 30% and 60% of patients with epilepsy have not achieved adequate control with current medications, and side effects are a significant problem. In the past 2 years, three drugs for epilepsy have been approved. At least six more drugs are in the final stages of development, and there is an active "pipeline." None of the new drugs are panceas, but many have special advantages and meet important specific needs. Felbamate, despite a high incidence of aplastic anemia and hepatic failure, remains useful because of its lack of sedative effects and high efficacy. Gabapentin is remarkable for its favorable side effect profile, lack of interactions, and straightforward kinetics. Lamotrigine is also nonsedating and may be especially useful in generalized epilepsies. Topiramate and vigabatrin are both highly effective, although each is associated with a variety of cognitive or psychiatric side effects that may limit utility. Oxcarbazepine shares the efficacy of carbamazepine, with fewer side effects or drug interactions. Zonisamide seems to be effective and cause mild side effects, although the risk for renal stones indicates a need for cautious use. Tiagabine, like gabapentin, is a mild drug with a favorable side effect profile. New forms of old drugs will make for easier administration; fosphenytoin will increase the safety of parenchymal phenytoin use. The best of the new drugs help, at most, 10% of previously uncontrolled patients to become seizure-free. The development of new drugs remains an important need.

Animals↗
PubMed1998

[A case of non-photosensitive, self-induced epileptic seizures with pacygyria].

We report an 11-year-old boy with a non-photosensitive epileptic self-induced seizures, pacygyria and familial ataxia. His grandmother and aunts had dysarthria, and his mother had developed progressive ataxia and myoclonus since 40 years old. His older sister had ataxia, mental retardation and epilepsy. As for the boy, motor developmental delay with muscle hypertonicity of left extremities was recognized at the age of 5 months. Mental retardation and ataxia was recognized at the age of 3 years and slight mental regression is recognized at the age of 11 years. No special findings were detected in an examination of his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain magnetic resonance imaging revealed pachygyria of the right cerebral cortecies. At the age of two, he began to induce seizures with impairment of consciousness in himself by waving his right hand over his face which was directed toward a source of bright light. At the age of seven, he developed spontaneous seizures with impairment of consciousness. An EEG showed frequent spikes in the occipital areas, on the right and left sides occurring either independently or synchronously. Intermittent photic stimulation and pattern stimulation did not induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the seizures was the occipital lobe. Treatment with valporate and zonisamide was effective in reducing the seizures. The findings of our case imply the pathogenesis of self-induced seizures and the relationship between PME and neuronal migration disorders.

Ataxia↗
PubMed1998

[Influence of co-administered antiepileptic drugs on nitrazepam tolerance in mice].

In the treatment of epilepsy, benzodiazepines are often administered in combination with other antiepileptic drug (s) because of the development of tolerance. In this study, the influence of concurrently administered antiepileptic drugs on tolerance to the anticonvulsant action of the nitrazepam (NZP) was studied using an animal tolerance model. Mice were given vehicle, NZP alone or NZP concurrently with one of six antiepileptic drugs (carbamazepine CBZ, phenytoin PHT, zonisamide ZNS, vigabatrin VGB, lamotrigine LTG, or flunarizine FNR) twice daily for 5 days. Tolerance was assessed by the ability of NZP to prevent pentylenetetrazol-induced clonic convulsions. Tolerance developed in mice treated with NZP alone, NZP plus CBZ, PHT, ZNS, VGB or LTG. On the other hand, mice receiving NZP + FNR showed no tolerance; there was no significant difference in seizure frequency between the vehicle group and NZP + FNR group. These data suggest that co-administration of FNR but not CBZ, PHT, ZNS, VGB or LTG may delay if not prevent development of tolerance to the anticonvulsant action of benzodiazepines.

Animals↗
PubMed2005

Analysis of antiepileptic drugs in biological fluids by means of electrokinetic chromatography.

An overview of the electrokinetic chromatographic methods for the analysis of antiepileptic drug levels in biological samples is presented. In particular, micellar electrokinetic capillary chromatography is a very suitable method for the determination of these drugs, because it allows a rapid, selective, and accurate analysis. In addition to the electrokinetic chromatographic studies on the determination of antiepileptic drugs, some information regarding sample pretreatment will also be reported: this is a critical step when the analysis of biological fluids is concerned. The electrokinetic chromatographic methods for the determination of recent antiepileptic drugs (e.g., lamotrigine, levetiracetam) and classical anticonvulsants (e.g., carbamazepine, phenytoin, ethosuximide, valproic acid) will be discussed in depth, and their pharmacological profiles will be briefly described as well.

Acetazolamide↗
PubMed2006

A case of Moebius syndrome presenting with congenital bilateral vocal cord paralysis.

We describe a female infant with bilateral facial paralysis and abducens palsy. To the best of our knowledge, this is the first report of Moebius syndrome presenting with congenital bilateral vocal cord paralysis (CBVCP). Although CBVCP can be part of a recognizable syndrome, i.e. Down syndrome, 22q deletion syndrome, Robinow's syndrome and cerebro-oculo-facio-skeletal syndrome, no reports of Moebius syndrome with CBVCP were found in the literature. CBVCP is often associated with central nervous system abnormalities. However, our patient had no detectable brain abnormalities. The etiology of Moebius syndrome remains unknown. It is interesting that the clinical manifestations of Moebius syndrome can include CBVCP. However, the pathophysiology of CBVCP is unknown and further investigations into the etiology of Moebius syndrome are required.

Anticonvulsants↗
PubMed2004

Anticonvulsant drugs in primary headaches prophylaxis.

Anticonvulsant drugs have been used in migraine prophylaxis since 1970. In recent years, new antiepileptic medications have given rise to much interest in pain control. Primary headaches prophylaxis is still based on old drugs, and physicians facing these conditions are always prompted to use any new possible choice. Among primary headaches, the most studied drug over last 15 years was divalproex sodium, and many papers showed its efficacy in the treatment of migraine headaches. Valproate is well tolerated and many dosages have been used with success. For the newer drugs, such as gabapentin, lamotrigine or topiramate, evidence is less strong but has been rapidly increasing in the last 5 years. In particular, topiramate has much more evidence of a good efficacy and a safe profile. We review the principal characteristics of their use, according to dosages, lasting of treatments, side effects and significant efficacy.

Amines↗
PubMed2002

New antiepileptic drug therapies.

The introduction of these new antiepileptic drugs, from felbamate to levetiracetam, raised hope of control of epilepsy with fewer adverse effects and improved quality of life. Unfortunately, many patients continue to experience refractory epilepsy despite the use of these new agents, and dose-related adverse effects and idiosyncratic reactions continue to be problematic. A recent report describes six new compounds in preclinical development, and five in clinical trials [131]. As the number of available, effective, but imperfect antiepileptic drugs increases, many challenges remain. These include: choosing the drug appropriate for the epileptic syndrome, assessing accurately the range of a drug's adverse effects in an individual patient, and considering carefully the drug's interactions in combination drug therapy. In considering drug combinations, differing mechanisms of drug action and favorable pharmacodynamic interactions (an area requiring additional studies) are of importance. Clinicians caring for children who have epilepsy anticipate further advances in the pharmacogenetics and molecular pathophysiology of epilepsy, leading to individually tailored, effective, and safe therapy.

Acetates↗
PubMed2000

Running down phenomenon and acute interictal psychosis in medial temporal lobe epilepsy.

PURPOSE: To examine the relationship between presurgical acute interictal psychosis and postsurgical running down phenomenon in a strictly homogeneous group with medial temporal lobe epilepsy. METHODS: Forty patients with mesial temporal sclerosis and an ultimate excellent surgical outcome, were divided into running down positive and negative groups. Various clinical and laboratory data, including presurgical psychotic episodes, were analyzed in the two groups. RESULTS: Patients in the running down positive group exhibited a significantly high incidence of presurgical history of acute interictal psychosis. CONCLUSION: We hypothesize that areas of secondary epileptogenesis beyond the scope of the primary epileptogenic zone, suggested by postsurgical running down phenomenon, may play an important role in the blockage and shift of the habitual propagation of seizure activity from the primary epileptogenic zone, to which Wolf attributed acute interictal psychosis.

Adult↗
PubMed1984

Nonlinear pharmacokinetics of CI-912 in adult epileptic patients.

We studied the pharmacokinetics of CI-912 (1,2-benziosoxazole-3-methanesulfonamide) in 10 adults with refractory partial seizures during an open-label pilot study. Plasma and whole blood concentrations were measured by a high-performance liquid chromatograph method after a single dose and up to and at steady state with one or two dosage regimens. Steady-state clearances averaged only 42% (range 20-60%) of single-dose clearances. Vm and Km values of the Michaelis-Menten equation were calculated for 9 of the 10 patients by a new method: Vm averaged 1,272 (range 500-1,973) mg/day and Km averaged 25.1 (range 9.23-52.5) micrograms/ml. The best initial dosage for a new patient is 300 mg CI-912 every 12 h.

Adult↗
PubMed1985

Blood-brain barrier transport of CI-912: single-passage equilibration of erythrocyte-borne drug.

Brain capillary transit of CI-912 was studied in vivo after a single capillary transit by the intracarotid injection technique. Brain permeability of 14C-drug was measured relative to that of tritiated water, a highly diffusible reference substance. The brain uptake index of CI-912 was measured at concentrations ranging from 5 to 400 micrograms/ml in different regions of the rat brain. Brain uptake was not via a saturable, carrier-mediated mechanism, but was attributable to lipid-mediated transport. The octanol/saline partition coefficient determined in vitro was 3.9, and the blood-brain barrier permeability times surface area product was 0.26 ml min-1 g-1 (in vivo). In the rat brain, efflux of CI-912 after intracarotid injection was found to be minimal, suggesting that this drug is retained in brain tissues. This drug is weakly bound to plasma proteins (75-79% of the drug is freely dialyzable in 4% human serum albumin at 5 micrograms/ml), and protein binding does not affect brain uptake. In contrast, the drug is highly bound to erythrocytes. At concentrations that approximate the predicted optimum therapeutic range (6-40 micrograms/ml), it has been demonstrated that in addition to exchange of plasma-borne drug, erythrocyte-borne CI-912 is able to equilibrate across the blood-brain barrier in the course of a single transcapillary transit. Approximately one half of the drug gaining access to brain in a single transcapillary passage is erythrocyte-borne.

Animals↗
PubMed1988

The structure of (1,2-benzisoxazol-3-yl)methanesulfonamide: a novel antiepileptic drug.

C8H8N2O3S, Mr = 212.54, monoclinic, P2(1)/a, a = 7.347 (9), b = 13.237 (4), c = 10.128 (8) A, beta = 108.916 (6) degree, V = 931.9 (1) A3, Z = 4, Dm = 1.52 (4), Dx = 1.514 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 28.35 cm-1, F(000) = 440, room temperature, R = 0.040 for 1864 observed reflections. The sulfonamide N forms intermolecular hydrogen bonds with the benzisoxazole ring N and also with the O on the sulfonamide group. Centrosymmetrically related benzisoxazole ring pairs are pi bonded with a high degree of overlap.

Anticonvulsants↗
PubMed2006

Comorbidity of eating disorders with bipolar disorder and treatment implications.

OBJECTIVES: To review the scientific evidence examining the comorbidity among eating disorders and bipolar disorder (BD). METHODS: We reviewed all published English-language studies addressing the comorbidity of anorexia nervosa, bulimia, bulimia nervosa, and binge eating disorder in patients with BD and studies of comorbidity of BD in patients with eating disorders. In addition, we discuss the pharmacologic treatment implications from reviewed studies of agents used in BD and eating disorders. RESULTS: Community and clinical population studies of the lifetime prevalence rates of eating disorders in patients with BD, and of BD in patients with eating disorders, particularly when subthreshold and spectrum manifestations of these disorders are included, indicate high rates of comorbidity among these illnesses. CONCLUSIONS: Pharmacologic treatment approaches to patients with BD and a co-occurring eating disorder require examination of the possible adverse effects of the treatment of each syndrome on the other and attempts to manage both syndromes with agents that might be beneficial to both.

Antidepressive Agents↗