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)

d-Tubocurarine (d-TC) is a drug commonly used to produce muscle paralysis. Although it has been demonstrated to produce seizures when injected directly into the cerebral ventricles, no lasting neurotoxic effects have been reported. Data presented here suggest that amounts of d-TC as small as 1 microgram injected directly into rat hippocampus resulted in selective damage to dentate granule cells. Larger doses (5 to 10 micrograms) induced limbic and motor seizures with damage to hippocampal pyramidal cells. Other brain regions showed a differential sensitivity to direct injections. Pharmacologic studies suggest a nicotinic mechanism for both actions. The neurotoxic effects could not be elicited if d-TC was administered systemically, even when the blood-brain barrier was disrupted.
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PMID:d-Tubocurarine causes neuronal death when injected directly into rat brain. 400 4

d-Tubocurarine (dtc) administered intracerebroventricularly (icv) to rats produced seizures. Gamma-aminobutyric acid (GABA) administered icv or hydroxylamine administered intraperitoneally (ip) protected the rats from dtc-induced seizures. GABA administered (ip) was ineffective. Local application of dtc to the spinal cord in decerebrate dogs produced facilitation of the scratch reflex. Application of GABA to the spinal cord inhibition the scratch reflex. It is thus concluded that the excitatory effects of dtc on the CNS may be through inhibition of naturally occurring inhibitory substances such as GABA or a closely related compound.
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PMID:Antagonism of some central effects of d-tubocurarine by gamma-aminobutyric acid. 721 72

Nicotinic acetylcholine receptors are important for maintaining optimal memory performance. In order to more fully characterize the involvement of nicotinic systems in memory, the contributions of nicotinic acetylcholine receptor subtypes were investigated. This study targeted the alpha 7 and alpha 4 beta 2 nicotinic receptors in the ventral hippocampus, an area known to be important for spatial working memory. Antagonists of alpha 7 and alpha 4 beta 2 receptors were locally infused into the ventral hippocampus of rats and the effects on memory were examined with the radial-arm maze. The subtype-specific competitive antagonists infused into separate groups of rats were methyllycaconitine citrate (an alpha 7 antagonist) and dihydro-beta-erythroidine hydrobromide (an alpha 4 beta 2 antagonist). Their effects on radial-arm maze performance were contrasted with the non-specific competitive antagonist, D-tubocurarine chloride. Significant deficits in radial-arm maze choice accuracy performance were found at 78.7 micrograms/side for methyllycaconitine and at 106.9 micrograms/side for dihydro-beta-erythroidine. Increased response latency was also seen at these doses. Tubocurarine induced seizures at doses previously reported to have no effect. Wet dog shakes were seen in most rats at 0.1 microgram/side with tubocurarine, 26.3 micrograms/side with methyllycaconitine and 106.9 micrograms/side with dihydro-beta-erythroidine. This study suggests that both alpha 7 and alpha 4 beta 2 nicotinic acetylcholine receptor subtypes are involved in working memory formation and that the hippocampus is a critical site for nicotinic cholinergic involvement in memory function, though the high doses of antagonists needed to produce the memory impairment may have had less than completely specific effects.
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PMID:Nicotinic antagonist administration into the ventral hippocampus and spatial working memory in rats. 933 Mar 63

The possibility of using polysorbate 80-coated polybutylcyanoacrylate nanoparticles to deliver low molecular polar hydrophilic drugs to the CNS has been studied. Tubocurarine (a quaternary ammonium salt) does not penetrate the normal intact blood-brain barrier. However, the injection of this drug directly into the cerebral ventricles of the brain provokes the development of epileptiform seizures as assessed by electroencephalogram (EEG). An in situ perfused rat brain technique was used as an experimental technique together with a simultaneous recording of the EEG. Nanoparticles were prepared by butylcyanoacrylate polymerization in an acidic medium. Fifteen minutes after the introduction of tubocurarine-loaded polysorbate 80-coated nanoparticles into the perfusate, epileptiform spikes in the EEG appeared. Intraventricular injection of tubocurarine caused the appearance of the EEG seizures 5 min after administration. Neither tubocurarine solution nor tubocurarine-loaded nanoparticles without polysorbate 80 or a mixture of polysorbate 80 and tubocurarine were able to influence the EEG. Thus only the loading of tubocurarine onto the polysorbate 80-coated nanoparticles appears to enable the transport of this quaternary ammonium compound through the blood-brain barrier.
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PMID:Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study. 946 8