Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of respiratory depression following treatment of prolonged seizures with benzodiazepines is variable in the literature. We retrospectively reviewed the charts of children treated for prolonged seizure over a one year period. Of the 56 seizures treated, 30 received lorazepam, 19 diazepam, and seven both drugs. Twenty two episodes (39%) of prolonged seizure were treated with multiple doses of benzodiazepines. In eight events (14%), there was documented respiratory depression following the administration of one or more doses of benzodiazepine; in six of these, multiple doses were given. The doses used were often at the low end or less than the recommended dose for treatment of status epilepticus. These data support suggestions that multiple doses of benzodiazepines increase the risk of respiratory depression.
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PMID:Respiratory depression in the acute management of seizures. 1219 34

Several neurotransmitters, including GABA acting at presynaptic GABA(B) receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABA(B) receptor-mediated heterosynaptic depression among populations of mossy fibers. This was accompanied by a decrease in the sensitivity of mossy fiber transmission to the exogenous GABA(B) receptor agonist baclofen. Autoradiography revealed a reduction in GABA(B) receptor binding in the stratum lucidum after status epilepticus. Failure of GABA(B) receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus.
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PMID:Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus. 1467 2

Diffusion-weighted nuclear magnetic resonance (NMR) imaging (DWI) is sensitive to the random translational motion of water molecules due to Brownian motion. Although the mechanism is still not completely understood, the cellular swelling that accompanies cell membrane depolarization results in a reduction in the net displacement of diffusing water molecules and thus a concomitant reduction in the apparent diffusion coefficient (ADC) of tissue water. Cerebral regions of reduced ADC appear hyperintense in a DWI and this technique has been used extensively to study acute stroke. In addition to cerebral ischemia, reductions in the ADC of cerebral water have been observed following cortical spreading depression, ischemic depolarizations (IDs), transient ischemic attack (TIA), status epilepticus, and hypoglycemia. Although the mechanism responsible for initiating membrane depolarization varies in each case, the ensuing cell volume changes follow a similar pattern. Water ADC values are also affected by the presence and orientation of barriers to translational motion (such as cell membranes and myelin fibers) and thus NMR measures of anisotropic diffusion are sensitive to more chronic pathological states where the integrity of these structures is modified by disease. Both theoretical prediction and experimental evidence suggest that the ADC of tissue water is related to the volume fraction of the interstitial space via the electrical conductivity of the tissue. The implication is that acute neurological disorders that exhibit electrical conductivity changes should also exhibit ADC changes that are detectable by DWI. A qualitative correlation between electrical conductivity and the ADC of water has been demonstrated in a number of animal model studies and the results indicate that reduced ADC values are associated with reductions in the extracellular volume fraction and increased extracellular tortuosity. The close relationship between ADC changes and cell volume changes in various pathological states suggests that NMR measurements are also sensitive to chemical communication between cells through the extracellular space (i.e., extrasynaptic or volume transmission, VT).
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PMID:Nuclear magnetic resonance (NMR) measurement of the apparent diffusion coefficient (ADC) of tissue water and its relationship to cell volume changes in pathological states. 1518 24

The pharmacological exploitation of the galanin receptors as drug targets for treatment of epilepsy, depression, and pain has been hampered by the lack of workable compounds for medicinal chemists from random screening of large chemical libraries. The present work uses the tripeptidomimetic galnon and displays its presumed pharmacophores on a rigid molecular scaffold. The scaffold is related to marine natural products and presents three functional groups near one another in space, in a manner reminiscent of a protein surface. An active compound, Galmic, was identified from a small synthetic library and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. Galmic has micromolar affinity for GalR1 receptors (Ki = 34.2 microM) and virtually no affinity for GalR2 receptors. In vitro, Galmic, like galanin, suppresses long-term potentiation in the dentate gyrus; it blocks status epilepticus when injected intrahippocampally or administered i.p. Galmic applied i.p. shows antidepressant-like effects in the forced-swim test, and it is a potent inhibitor of flinching behavior in the inflammatory pain model induced by formalin injection. These data further implicate brain and spinal cord galanin receptors as drug targets and provide an example of a systemically active compound based on a scaffold that mimics protein surfaces.
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PMID:Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure, pain, and forced-swim tests. 1524 Aug 75

Epilepsy features, psychiatric profile, psychosocial factors, and outcome are described for six children (three males) aged 5-15 years (mean 12.1) with psychogenic status epilepticus (PSE), i.e., prolonged or repetitive psychogenic seizures (PSs), >30 minutes, simulating status epilepticus. They had epilepsy, they were on chronic anticonvulsants (ACVs), and some had other neurological deficits. All received intravenous and/or rectal ACVs prior to suspicion of PSE. PSE was confirmed via video/EEG, demonstrating no epileptogenic activity during alleged seizures. Provocation and placebo therapy techniques were used in two. Psychiatric assessment identified comorbid disorders such as depression, anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, and posttraumatic stress disorder. Psychosocial stressors were almost ubiquitous. Psychiatric intervention included psychotherapy, family therapy, and medical treatment in one patient. Outcome was monitored for an average of 3.6 years (3-5 years). PSE did not recur. PSs recurred in three. Psychiatric comorbidity improved in four, who accepted psychiatric intervention and whose epilepsy also improved. In conclusion, the occurrence of PSE in children and adolescents with epilepsy is stressed. Prompt diagnosis was often missed in the acute care setting, and this carries important implications for iatrogenic complications. PSE diagnosis resulted in identification and management of comorbid psychiatric disorders. This was probably important in reducing the predominating anxiety and affective disorders in most patients as well as PSE recurrence. Epilepsy severity and associated deficits were most likely important factors in determining outcome.
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PMID:Psychogenic status epilepticus in children. 1525 92

Cocaine abuse may lead to overdose (related to seizures and/or status epilepticus) and to diseases (schizophrenia, depression, and anxiety). This work was designed to study the influence of drugs used to treat psychopathologies associated with cocaine abuse on cocaine-induced seizures and mortality in mice. Fluoxetine (10, 20, 40 mg/kg), imipramine and buspirone (5, 10 mg/kg), pimozide (10, 20 mg/kg), lithium (56.3, 112.5 mg/kg), and naltrexone (25, 50 mg/kg) were administered intraperitoneally, 30 minutes prior to cocaine (90 mg/kg, ip). The animals were observed (30 minutes) to determine: latency to first seizure, number of seizures, and number of deaths after cocaine overdose. Fluoxetine, imipramine, buspirone, and pimozide had pro- or anticonvulsant effects depending on the dose. Smaller doses protected and higher doses increased cocaine-induced seizures and/or mortality. Naltrexone worsened and lithium protected against seizures. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with cocaine addiction because of the possibility of potentiating cocaine toxicity.
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PMID:Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality. 1558 32

Venoms of spiders and wasps are well recognized to present high affinity to the central nervous tissue of many mammalian species. Here we describe the effects of direct exposure of rat (Rattus norvegicus) brains to the crude and denatured venom of the Brazilian social wasp Polybia ignobilis. Lower doses of crude venom injected via intracerebroventricular (i.c.v.) inhibited the exploratory activity of animals, while higher doses provoked severe generalized tonic-clonic seizures, with hind limb extension. The status epilepticus lasted for few minutes leading the animals to respiratory depression and death. In contrast, the denatured venom was anticonvulsant against acute seizures induced by the i.c.v. injection of bicuculline, picrotoxin and kainic acid, but it was ineffective against seizures caused by systemic pentylenetetrazole. Moreover, the [3H]-glutamate binding in membranes from rat brain cortex was inhibited by the denatured venom in lower concentrations than the [3H]-GABA binding. The denatured venom contains free GABA and glutamate (34 and 802 pg/microg of venom, respectively), but they are not the major binding inhibitors. These interactions of venom components with GABA and glutamate receptors could be responsible for the anticonvulsant effects introducing the venom from P. ignobilis as a potential pharmacological source of anticonvulsant drugs.
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PMID:Anticonvulsant effects of the wasp Polybia ignobilis venom on chemically induced seizures and action on GABA and glutamate receptors. 1595 69

The effects of two serotonergic (5-HT1A) receptor agonists (8-OH-DPAT; 0.01, 0.1, 0.3, 1 mg/kg, s.c., and Indorenate; 1, 3, 10 mg/kg, i.p.) were evaluated in three type of seizures in male Wistar rats: clonic-tonic convulsions induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.), status epilepticus (SE) of limbic seizures produced by kainic acid (KA, 10 mg/kg, i.p.) and tonic-clonic seizures by amygdala kindling. 8-OH-DPAT decreased the incidence of tonic seizures and the mortality rate induced by PTZ. Indorenate increased the latency to the PTZ-induced seizures and decreased the percentage of rats showing tonic extension and death. Concerning KA, 8-OH-DPAT augmented the latency and reduced the frequency of wet-dog shake (WDS) and generalized seizure (GS). At high doses it diminished the occurrence and delayed the establishment of SE. Indorenate augmented the latency to WDS, GS and SE, and diminished the number of GS. 8-OH-DPAT and Indorenate did not alter the expression of kindled seizures. However, Indorenate enhanced the refractoriness to subsequent seizures during the postictal depression. Some effects induced by 8-OH-DPAT and Indorenate on seizures evaluated and postictal depression were fully or partially blocked by WAY100635. These results suggest that 5-HT1A receptor agonists modify epileptic activity depending on the type of seizure.
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PMID:5-HT1A receptor agonists modify epileptic seizures in three experimental models in rats. 1599 34

We examined efficacy of continuous midazolam (MDL) infusion in seven episodes of refractory nonconvulsive status epilepticus (NCSE) in five children. Diagnosis included Lennox-Gastaut syndrome (two cases), and symptomatic generalized epilepsy, ring chromosome 20 syndrome, and epilepsy with continuous spike-waves during slow-wave sleep (one case each). One patient with Lennox-Gastaut syndrome and another with ring chromosome 20 syndrome had two episodes of NCSE. MDL was given as an initial bolus of 0.15 to 0.3 mg/kg, followed by continuous intravenous infusion at 0.1 to 0.2 mg/kg/hr. The infusion rate was increased slowly by 0.1 mg/kg/hr every 0.5 to 1.0 hr, up to 0.4 mg/kg/hr or until NCSE was controlled. The electroencephalogram, vital signs, blood pressure, and oxygen saturation were monitored during therapy. Electrical status epilepticus was abolished within a few hours in five of the seven episodes, and two patients could maintain wakefulness, oral intake, and bowel and bladder control throughout the continuous infusion. In one patient in whom NCSE recurred, it then remained uncontrolled even at a maximum dose. Serious complications such as respiratory depression or hypotension were not observed. Continuous intravenous infusion of MDL was effective and safe for NCSE in children, and can be used as firstline therapy for this condition.
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PMID:[Continuous midazolam infusion for refractory nonconvulsive status epilepticus in children]. 1616 41

Both the incidence and prevalence of epilepsy are high among the elderly. Cerebrovascular disease is the most common underlying cause, although as many as 25-40% of new epilepsy cases in the elderly have no obvious underlying etiology. Status epilepticus appears to occur more frequently in individuals greater than 60 years, and the morbidity and mortality of status epilepticus are significantly greater in this age group. Elderly patients with seizures, particularly complex partial seizures, present differently than younger adults, which can lead to misdiagnosis. Post-ictal confusion may last as long as 1-2 weeks in an elderly patient, as opposed to minutes in younger individuals. Adverse events are similar in symptomatology, but are more common in elderly patients and occur at lower doses and plasma drug concentrations. Neuropsychiatric disorders, such as depression and anxiety, are common in elderly patients with epilepsy, although often under-diagnosed and inadequately treated. The risk of osteoporosis is high among elderly women taking antiepileptic drugs, which underscores the importance of assessing bone health and treatment in this group. Management of the older patient with epilepsy requires an understanding of the etiologies and the medical and psychological aspects unique to this age group.
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PMID:Epidemiological and medical aspects of epilepsy in the elderly. 1638 89


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