Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Status epilepticus, prolonged intermittent or continuous seizure activity lasting 30 min or longer, is associated with high morbidity and mortality. The longer a seizure persists, the more refractory to treatment it becomes. The pilocarpine model of status epilepticus in rodents develops refractoriness to many first-line treatments as seizure duration increases, rendering it a good model to study refractory status epilepticus. This study was initiated to study the development of refractoriness of pilocarpine-induced status epilepticus to diazepam. Early pilocarpine-induced status epilepticus responded rapidly to diazepam treatment, whereas status epilepticus of longer duration became increasingly less responsive to treatment. Dizocilpine maleate-pretreated animals responded rapidly to diazepam treatment, even after 60 min of status epilepticus. Animals administered dizocilpine maleate at 15, 30 or 60 min after the onset of status epilepticus also demonstrated a rapid response to diazepam compared to pilocarpine-alone-treated animals. The longer the status epilepticus progressed prior to dizocilpine maleate injection, the longer the status epilepticus lasted after diazepam treatment. However, in all cases where dizocilpine maleate was administered, one injection of diazepam was able to terminate the status epilepticus, in contrast to the animals that did not receive dizocilpine maleate, in which the seizure was only attenuated. The results indicate that N-methyl-D-aspartate receptor activation plays a role in the seizure-induced refractoriness to benzodiazepines in status epilepticus, and blocking N-methyl-D-aspartate receptor activation converts refractory status epilepticus to a seizure responsive to benzodiazepine therapy. These findings offer insights into developing novel therapeutic interventions to improve the treatment of status epilepticus. Understanding the molecular mechanisms that mediate the effects of N-methyl-D-aspartate receptor activation on the development of resistance to treatment in status epilepticus will provide rational insights into more rapid methods to terminate seizure activity in this condition.
 ...
PMID:N-methyl-D-aspartate receptor activation regulates refractoriness of status epilepticus to diazepam. 1043 Apr 76

Dizocilpine maleate (MK-801) is a highly potent, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Although it has been suggested that dizocilpine may be beneficial in alleviating some symptoms of ethanol withdrawal, a rigorous evaluation of beneficial versus detrimental (phencyclidine-like) actions has not been done. The objective of the present investigation was to explore whether dizocilpine protects against ethanol withdrawal-induced increases in seizure susceptibility without being compromised by its phencyclidine-like behavioral actions. The effects of dizocilpine were assessed by using seizure threshold determinations and scoring of open field behaviors. Low dose dizocilpine administration preferentially protected against bicuculline seizure induction in ethanol-withdrawn female rats when compared with findings in ethanol-withdrawn male rats. In contrast, we found dramatic reductions in dizocilpine-induced open field behaviors during ethanol withdrawal in both male and female rats compared with findings for pair-fed control animals. [3H]MK-801 binding analysis ruled out changes in cerebral cortex or hippocampus receptor density or affinity as having a primary role in these differential responses. Taken together, our findings from these studies indicate that there are complex neuroadaptations in NMDA receptor systems after persistent ethanol exposure, manifested as either enhanced or reduced responses, depending on the measure used.
 ...
PMID:Altered responses to dizocilpine maleate administration in ethanol-withdrawn male and female rats. 1245 39