Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy

Ault, Brian; Olney, Melinda A.; Joyner, Judson L.; Boyer, Charles E.; Notrica, M; Soroko, Francis E.; Wang, Ching M.

doi:10.1016/0006-8993(87)90428-8

Cited by 72 publications

(32 citation statements)

References 51 publications

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“…Methylxanthines are used clinically as a diuretic, circulatory and respiratory stimulant, and treatment for headaches. The convulsive properties of methylxanthines have been well documented (14,15,29). Intoxication with caffeine and theophylline can lead to seizures at plasma concentrations Ͼ 100 M (30).…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] C-labeled ascorbic acid was oxidized to 1-14 C-labeled DHA by the addition of ascorbate oxidase (125 U/mL H 2 O) and measured by HPLC as described (21). After a 15-s incubation of 50 L of erythrocyte suspension with 50 L of 1-14 C-labeled DHA (10 and 25 M, 8 Ci/mL) at 4°C (in the presence or absence of 3 mM caffeine), the uptake was terminated by the addition of ice-cold stop solution.…”

Section: Patient 15 (Female 8 Y)mentioning

confidence: 99%

“…Data from four patients with individual mutations in the GLUT1 gene are discussed: patient 1 (hemizygosity), 3 (S66F), 15 (368Ins23), and 17 (R333W). Zero-trans influx of 14 C-labeled 3-O-methyl glucose (3-OMG) into erythrocytes of patients is reduced (patient 1, 51%; 3, 45%; 15, 31%; 17, 52%) compared with maternal controls. Inhibition studies on patients 1, 3, 17, and maternal controls show an IC 50 for caffeine of approximately 1.5 mM both in controls (n ϭ 3) and patients (n ϭ 3) at 5 mM 3-OMG concentration.…”

mentioning

confidence: 99%

“…Methylxanthine neurotoxicity includes potentially life-threatening convulsions (13). The proconvulsant actions of methylxanthines have been associated with their antagonistic properties to the adenosine receptors (14,15). Whether the inhibition of glucose transport by methylxanthines could potentiate the proconvulsant effects of these compounds is unclear.…”

mentioning

confidence: 99%

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Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Yang

Klepper

et al. 2001

Pediatr Res

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Section: Discussionmentioning

confidence: 99%

Section: Patient 15 (Female 8 Y)mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Yang

Klepper

et al. 2001

Pediatr Res

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“…This increase in excitability is reminiscent of the action of theophylline, which induced spontaneous activity under the same conditions. There is a great probability that this feature is related to the well-known epileptogenic action of this drug in humans (2). Thus, there is a major difference in the effects of fenbufen and quinolones on hippocampal activity.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal activity in the presence of quinolones and fenbufen in vitro

Dimpfel¹,

Spüler²,

Dalhoff³

et al. 1991

Antimicrob Agents Chemother

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Rare side effects on the central nervous system including dizziness, restlessness, and even very rare convulsions as reported during the course of antibiotic treatment with quinolones were the topic of a well-controlled in vitro approach. The excitability of brain matter was tested by electrically evoking field potentials in the CA1 region of the rat hippocampus in vitro. Direct effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were found to occur as a dose-dependent increase in amplitude of this field potential, which is in line with the view that the quinolones increase excitability. The highest increase was found with enoxacin and nalidixic acid, and the lowest increase was found with ciprofloxacin. In order to keep the potential risk of the antibiotic therapy as low as possible, ciprofloxacin might be the drug of choice of the quinolones. In contrast to the quinolones, which only increased the amplitudes of electrically evoked potentials, fenbufen induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. (9,11,15,17).However, the concentrations needed for an interaction of quinolones and GABA are rather high and vary among the different quinolones tested by a factor of -100. These differences, recorded in the specific receptor binding and competition in in vitro experiments, do not mirror clinical experience with the various quinolones, as the total incidences of CNS effects are on the average 0.4 to 1.6% (1,5,7,10,16 (3,14). These data indicate, first, that GABA-ergic mechanisms are a necessary but not sufficient prerequisite for effects and, second, that specific ligand receptor studies do not reflect the complex mechanism leading to quinolone-mediated CNS excitation.The aim of the present investigation was to test the ability of different quinolones alone and in combination with fenbufen to influence electrically evoked field potentials in the hippocampal slice preparation. The method of using brain tissue slices as physiologically intact units dates back to 1966 (18). In this ex vivo model, the complex physiology, i.e., the interconnections between neurons as well as between neurons and glial cells is maintained. In the meantime, this technique has been widely used in order to study the physiology of the hippocampus in vitro (for review, see reference 13). The modulatory contribution, especially, of various transmitters to hippocampal excitation and inhibition phenomena could be studied on a cellular level but within the pertinent network (6).(Part of this study has been presented in abstract form at the 3rd International Symposium on New Quinolones, Vancouver, Canada, 1990.) MATERIALS AND METHODS Hippocampal slice preparations were obtained from 15 adult male CD rats (Charles River Wiga). The animals were exsanguinated under slight ether anesthesia, the brain was removed in total, and the hippocampal formation was isolated under microstereoscopic sight. The...

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Ketogenic Dietary Therapy in Africa

Toit¹

2012

Dietary Treatment of Epilepsy: Practical Implementation of Ketogenic Therapy

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Pro-convulsant actions of theophylline and caffeine in the hippocampus: implications for the management of temporal lobe epilepsy

Cited by 72 publications

References 51 publications

Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Glucose Transporter Type 1 Deficiency Syndrome (Glut1DS): Methylxanthines Potentiate GLUT1 Haploinsufficiency In Vitro

Hippocampal activity in the presence of quinolones and fenbufen in vitro

Ketogenic Dietary Therapy in Africa

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