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Life-threatening diphenhydramine toxicity presenting with seizures and a wide complex tachycardia improved with intravenous fat emulsion.

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Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for

Quinine, a blocker of neuronal cx36 channels, suppresses seizure activity in rat neocortex in vivo.

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OBJECTIVE The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the

Thalamic modulation of cingulate seizure activity via the regulation of gap junctions in mice thalamocingulate slice.

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The thalamus is an important target for deep brain stimulation in the treatment of seizures. However, whether the modulatory effect of thalamic inputs on cortical seizures occurs through the modulation of gap junctions has not been previously studied. Therefore, we tested the effects of different

Fluorocitrate-mediated astroglial dysfunction causes seizures.

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A role for astroglia in epileptogenesis has been hypothesised but is not established. Low doses of fluorocitrate specifically and reversibly disrupt astroglial metabolism by blocking aconitase, an enzyme integral to the tricarboxylic acid cycle. We used cerebral cortex injections of fluorocitrate,

Anticonvulsant actions of gap junctional blockers in an in vitro seizure model.

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Gap junctions (gjs) are increasingly recognized as playing a significant role in seizures. We demonstrate that different types of gap junctional blocking agents reduce the duration of evoked seizure-like primary afterdischarges (PADs) in the rat in vitro CA1 hippocampal pyramidal region, following

Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models.

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BACKGROUND Gap junctions are clusters of intercellular channels allowing the bidirectional pass of ions directly into the cytoplasm of adjacent cells. Electrical coupling mediated by gap junctions plays a role in the generation of highly synchronized electrical activity. The hypersynchronous

Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists.

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A major issue in designing drugs as antagonists at the glycine site of the NMDA receptor has been to achieve good in vivo activity. A series of 4-hydroxyquinolone glycine antagonists was found to be active in the DBA/2 mouse anticonvulsant assay, but improvements in in vitro affinity were not

Quantitative structure-anticonvulsant activity relationships of valproic acid, related carboxylic acids and tetrazoles.

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Valproic acid and several structurally related carboxylic acids and tetrazole analogues have been shown to antagonize seizures induced by pentylenetetrazole in mice. To investigate the influence of the alkyl substituents on the anticonvulsant activity, the octanol-water partition coefficients and

Modulation of burst frequency, duration, and amplitude in the zero-Ca(2+) model of epileptiform activity.

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Incubation of hippocampal slices in zero-Ca(2+) medium blocks synaptic transmission and results in spontaneous burst discharges. This seizure-like activity is characterized by negative shifts (bursts) in the extracellular field potential and a K(+) wave that propagates across the hippocampus. To

Modulation of gap junctional mechanisms during calcium-free induced field burst activity: a possible role for electrotonic coupling in epileptogenesis.

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To date, there is little experimental evidence supporting or refuting electrotonic interactions through gap junctions in the generation and/or spread of seizure activity in the mammalian brain. We have studied gap junctional mechanisms in the in vitro calcium-free induced model of epilepsy using

Transport of the beta-lactam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro.

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Peripherally administered beta-lactam antibiotics, which are structural analogs of tripeptides, may cause neurotoxic reactions or induce seizures. Previous in vivo studies provided evidence for brain uptake of these antibiotics. In the present work, we studied the extent and mechanism of the uptake

Neurotoxicity of non-ionic X-ray contrast media after intracisternal administration in rats.

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The neurotoxicity of an X-ray contrast medium appears inversely related to the hydrophilicity of the agent. To further test this hypothesis, four non-ionic X-ray contrast agents, differing in hydrophilicity, (ioversol, iopromide, iohexol and iopamidol) were injected into the cisternal magna of

pH Sensitivity of non-synaptic field bursts in the dentate gyrus.

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Under conditions of low [Ca(2+)](o) and high [K(+)](o), the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the

[Pharmacological characterization of novel pyridazines. Part 1: Physicochemical parameters, acute toxicity and action on the central nervous system (author's transl)].

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The author determined the distribution coefficients (in n-octanol/water) and the RM values (thin-layer chromatographically, using two solvent systems) of 17 newly synthetized pyridazines. These determinations evidenced that the majority of these compounds are relatively polar. Altogether the acute

Syntheses, calcium channel antagonist and anticonvulsant activities of substituted 1,4-dihydro-3,5-pyridinedicarboxylates containing various 3-alkyl ester substituents.

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A group of 3-alkyl 5-isopropyl 4-aryl-1,4-dihydro-2,6-dimethyl- 3,5-pyridinedicarboxylates 10-20 containing an amine, quaternary ammonium, aryl (heteroaryl)alkenyl, 4-(4-fluorophenyl)- piperazin-1-yl or methoxy moiety in the C-3 alkyl ester R-substituent in combination with a C-4 phenyl ring bearing

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