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)

Despite demonstrated differences in toxicity profiles between tricyclic antidepressants (TCAs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), no studies have examined hospital costs associated with acute antidepressant overdoses. Given the high incidence of such overdoses, it is important to examine treatment patterns and associated costs. This prospective, multicentre cohort study compared the hospital and physician costs associated with TCA and fluoxetine drug overdoses. Over a 30-month period, 622 consecutive patients with a fluoxetine or TCA overdose presented to the emergency departments, or were admitted to intensive care or medical units, of 9 participating medical centres across the US. Inclusion criteria were: ingestion of a single antidepressant (fluoxetine or a TCA), without clinically significant co-ingestants; laboratory confirmation of the overdose; and retrievable hospital bills. Patients were followed until discharge from the emergency department or hospital. Hospital and physician charges were collected from billing data. Hospital charges were adjusted using Health Care Financing Administration cost: charge ratios to estimate costs; physician charges were adjusted to estimate costs. Patient demographic and clinical data were prospectively gathered during the course of medical treatment. Clinical data recorded included level of consciousness, cardiopulmonary complications, vital sign or ECG abnormalities, agitation, seizures, CNS depression and death. 136 patients (121 with TCA overdose and 15 with fluoxetine overdose), representing 21.8% of the 622 patients entered, met the inclusion criteria. Mean length of stay varied from 0.73 [+/-standard error of the mean (SEM) 0.33] days for fluoxetine overdose patients to 3.59 (+/-SEM 0.48) days for TCA overdose patients (p = 0.038). Mean hospital costs were $US668 for patients with a fluoxetine overdose compared with $US4691 for those with a TCA overdose (p < 0.0001). No significant differences were observed between the TCA and fluoxetine overdose groups with regard to physician costs. Median hospital and physician costs increased from $US3029 to $US4396 from the first 15-month period of the study to the second 15-month period of the study for the TCA overdose group, but decreased from $US881 to $US396 for the fluoxetine overdose group. Patients with fluoxetine overdoses had lower hospital and total medical costs compared with patients with TCA overdoses. There was some evidence supporting a reduction in the medical costs of treating fluoxetine overdoses over the 30-month study period.
 ...
PMID:Acute medical costs of fluoxetine versus tricyclic antidepressants. A prospective multicentre study of antidepressant drug overdoses. 1016 26

Electroconvulsive therapy (ECT) is used to treat drug-resistant depressive disorders. The results of studies on the mechanism underlying the effectiveness of ECT on depression are still controversial. ECT stimulus is usually larger than the threshold of induction of seizures and activation of whole-brain is believed to be necessary to produce therapeutic effects. A single ECT session induces alterations of the electroencephalogram (EEG) including initial epileptic discharges, then slow waves, and finally flattened EEG. Repeated ECT results in an increasing number of slower waves in the EEG for as long as a month. ECT-induced changes in various neurotransmitter systems have also been reported. Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neurotransmitters involved in depressive illness, and ECT alters several 5-HT-receptor subtypes in the central nervous system. 5-HT1A receptors in post-synaptic neurons are sensitized by repeated ECT, but those in pre-synaptic neurons (auto-receptors) are not changed. In addition, our electrophysiological studies have shown that ECT increases sensitivity to 5-HT of 5-HT3 receptors in the hippocampus, resulting in an increase in release of neurotransmitters such as glutamate and gamma-aminobutyric acid. In contrast, ECT decreases the auto-receptor functions in noradrenergic and dopaminergic neurons in the locus coeruleus and substantia nigra, respectively, resulting in an increase in release of noradrenaline and dopamine. In conclusion, 5-HT1A-receptor sensitization may be important for explaining the effectiveness of ECT, as this change induces a decrease in the number of 5-HT2A receptors that are elevated in depressive patients. Facilitation of neurotransmitter releases due to 5-HT3-receptor sensitization by ECT may also play an important role in effective treatment of depressive patients refractory to therapeutic drugs.
 ...
PMID:Mechanism underlying the therapeutic effects of electroconvulsive therapy (ECT) on depression. 1046 62

Transgenic animal models can reconstruct cellular, biochemical, and molecular alterations associated with human diseases and may help identify key disease mechanisms. Gene disruption, which results in the loss of the functional gene product, is the most common genetic alteration generated by transgenic approaches. Gene disruption can be introduced by random transgene integration or by gene targeting. Both of these approaches have resulted in mice that display recurrent seizures reminiscent of epilepsy. Here, we briefly describe the techniques of random transgene insertion and gene targeting and discuss how these methods were used to generate the epileptic jerky and 5-hydroxytryptamine (5-HT2C) receptor deficient mice. We also analyze how these mutants can contribute to our understanding of the molecular and cellular mechanisms underlying epileptic seizures.
 ...
PMID:Transgenic approaches to epilepsy. 1051 21

Isatin (indole-2,3-dione) has been found in mammalian tissues as one of major components of tribulin, a postulated endogenous marker of stress and anxiety. I previously identified isatin as an endogenous inhibitor of monoamine oxidase (MAO) in the human urine and the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using GC-MS. A single dose of isatin significantly increased norepinephrine (NE) and 5-hydroxytryptamine (5-HT) concentrations measured 2 h later in the various brain regions of normotensive Wistar Kyoto rats (WKY). Striatal acetylcholine (ACh) and dopamine (DA) levels significantly increased 2 h after the administration of isatin. Perfused through a microdialysis probe, isatin also produced a significant and concentration-dependent increase in the ACh and DA concentration in the perfusate from the rat striatum. In the patients with Parkinson's disease, urinary isatin concentrations tended to increase according to the severity of disease, as classified by the Hoehn and Yahr criteria. Isatin significantly increased striatal DA levels in a rat model of Parkinson's disease. Isatin may play a role in the regulation of the brain levels of ACh and DA. Furthermore, isatin has a wide spectrum of biological properties: (a) a marker of stress and anxiety, (b) an inhibitor of a number of enzymes, (c) an anti-seizure agent, (d) an inhibitor of benzodiazepin receptors and ANP binding to its receptors.
 ...
PMID:[Pharmacological role of isatin, an endogenous MAO inhibitor]. 1077 57

Serotonin syndrome is an underreported complication of pharmacotherapy that has been relatively ignored in the medical literature. We discuss 2 recent cases seen at our institution and 39 cases described in the English-language literature since 1995. We found that patients with serotonin syndrome most often (74.3%) presented within 24 hours of medication initiation, overdose, or change in dosage. The most common presenting symptoms and signs were confusion, agitation, diaphoresis, tachycardia, myoclonus, and hyperreflexia. The prevalences of hypertension, coma/unresponsiveness, seizures, and death were not as prominent in our study as previously reported, perhaps reflecting earlier recognition and intervention. The most common therapeutic intervention was supportive care alone (48% of patients). The use of 5-hydroxytryptamine (5-HT) antagonists such as cyproheptadine, however, has become more common and might reduce the duration of symptoms. Only 1 death occurred, and most patients (57.5%) had complete resolution of their symptoms within 24 hours of presentation. The increased use of serotonergic agents (alone and in combination) across multiple medical disciplines presents the possibility that the prevalence and clinical significance of this condition will rise in the future. Internists will need to be increasingly aware of and prepared for this pharmacologic complication. Prevention, early recognition of the clinical presentation, identification and removal of the offending agents, supportive care, and specific pharmacologic therapy are all important to the successful management of serotonin syndrome.
 ...
PMID:Serotonin syndrome. Presentation of 2 cases and review of the literature. 1094 49

Peripheral administration of the 5-hydroxytryptamine (5-HT)(2C/1B) agonist 1-(m-chlorophenyl)piperazine (m-CPP) produces abnormal orofacial movements in rats. We have previously shown that this behavior is mediated by 5-HT(2C) receptors in the subthalamic nucleus [Neuroscience 72 (1996) 117]. The present studies examined this effect after serotonin depletion to determine whether removal of endogenous serotonin affected this behavioral response and/or subthalamic 5-HT(2C) receptors. Rats received an intraventricular infusion of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 100 mg/10 ml) or vehicle after desipramine pretreatment (25 mg/kg ip). The efficacy of serotonin depletion was confirmed by a decrease in serotonin uptake sites measured by autoradiography. Oral dyskinesia induced by peripheral administration of m-CPP (1.0 mg/kg ip) was markedly increased in lesioned rats compared to sham-operated controls 4 and 8 but not 12 days after the lesion. A subset of lesioned rats that displayed transient seizures after m-CPP injection did not prevent the measurement of oral dyskinesia during the observation period. No differences in 5-HT(2C) receptor levels were found with ligand-binding autoradiography in the subthalamic nucleus, or in other brain regions that express this receptor, in rats sacrificed 5 days following 5,7-DHT lesions. The data indicate that lesion of serotonergic neurons in adult rats induces a transient increase in motor responses mediated by subthalamic 5-HT(2C) receptors. These data suggest that functional alterations in serotonergic transmission in the subthalamic nucleus may be involved in the pathophysiology of hyperkinetic movement disorders.
 ...
PMID:Increased m-CPP-induced oral dyskinesia after lesion of serotonergic neurons. 1126 40

SB-243213 (5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline hydrochloride) is a new, selective 5-hydroxytryptamine (5-HT)2C receptor inverse agonist. SB-243213 has high affinity for the human 5-HT2C receptor (pK(i) 9.37) and greater than a 100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and ion channels. In in vitro functional studies, SB-243213 acted as an inverse agonist at the human 5-HT2C receptor with a pK(b) of 9.8. In in vivo studies, SB-243213 was a potent inhibitor of central 5-HT2C receptor-mediated function in rats, blocking meta-chlorophenylpiperazine-induced hypolocomotion with an ID50 of 1.1 mg/kg p.o. and a long duration of action (>8 h). In rats, SB-243213 exhibited anxiolytic-like activity in both the social interaction and Geller-Seifter conflict tests. Importantly, unlike diazepam, chronic administration of SB-243213 did not result in the development of either tolerance to the anxiolytic-like effects or withdrawal anxiogenesis. Furthermore, in rodents, SB-243213 did not affect seizure threshold, did not increase body weight or induce catalepsy, but attenuated the haloperidol-induced catalepsy. SB-243213 did not affect amphetamine-, MK-801- or phencyclidine-induced hyperactivity. In conclusion, SB-243213 may possess an improved anxiolytic profile compared to benzodiazepines. SB-243213 also modulates dopaminergic transmission, lacks pro-psychotic properties and may have utility in the treatment of schizophrenia and motor disorders.
 ...
PMID:SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety. 1148 55

Recent studies have shown the involvement of 5-hydroxytryptamine (5HT) in the pathogenesis of epilepsy. Hence it was decided to investigate the effect of the 5HT3 receptor antagonist ondansetron against maximal electroshock (MES)-induced seizures in rats. Also, the anticonvulsant activity of ondansetron in combination with phenytoin and its effect on the cognitive deficits induced by phenytoin were studied. MES was induced through ear-clip electrodes using a current strength of 150 mA for 0.2 second. The index of protection was taken as the inhibition of tonic hindlimb extension. The ED25 and ED16 doses of ondansetron were combined with subanticonvulsant doses of phenytion, i.e., 6 and 3 mg/kg. The retention latencies in the passive avoidance task (PAT) were assessed on Days 1 and 21 of chronic administration of ondansetron alone, phenytoin alone, and ondansetron in combination with phenytoin. The ED50 of ondansetron was found to be 1.05 (0.51-2.2) mg/kg. The combination of ondansetron with phenytoin had a potentiating effect against MES. Also, the retention latencies in the PAT of ondansetron alone and ondansetron in combination with phenytoin were significantly higher than that of phenytoin alone. Thus, ondansetron has potent anticonvulsant activity in rats and further potentiates the anticonvulsant activity of phenytoin. Also, it attenuates the cognitive dysfunction induced by phenytoin and merits further research for its mechanisms.
...
PMID:Anticonvulsant profile of ondansetron in rats. 1260 24

High doses of the muscarinic cholinergic agonist pilocarpine are a useful model for investigation of the essential mechanisms for seizure generation and spread in rodents. Pilocarpine (400 mg/kg; subcutaneously) was administered in 2-month-old female rats, and the content of striatum monoamines and (M(1)+M(2)) muscarinic and D(2) dopaminergic receptors was measured in the acute period. All treated animals showed peripheral cholinergic signs, stereotyped and clonic movements, tremors, seizures and the percentage mortality was approximately 63%. High performance liquid chromatography determinations, performed 24 h later, showed a decrease of striatal levels of dopamine, dihydroxyphenylacetic acid, 4-hydroxy-3-methoxy-phenylacetic acid and 5-hydroxytryptamine. Pilocarpine treatment induced downregulation of (M(1)+M(2)) muscarinic receptors and reduced the dissociation constants of (M(1)+M(2)) muscarinic and D(2) dopaminergic receptors, suggesting that these systems exert opposite effects on the regulation of convulsive activity. These and other important neurochemical changes found in the course of establishment of an epileptic focus can be observed after status epilepticus induced by pilocarpine.
 ...
PMID:Pilocarpine-induced seizures in adult rats: monoamine content and muscarinic and dopaminergic receptor changes in the striatum. 1455 91

The 5-hydroxytryptamine(6) (5-ht(6)) was one of the most recent additions to the 5-HT receptor family, selective antagonists have recently been developed and potential functional roles are now becoming apparent. The high affinity of a wide range of psychiatric drugs for the 5-ht(6)receptor, together with its almost exclusive expression in the CNS, being abundant in limbic and cortical regions, has stimulated significant research interest. The 5-ht(6)receptor appears to regulate glutamatergic and cholinergic neuronal activity, and increasing evidence suggests that it may be involved in the regulation of cognition, feeding and, possibly, affective state and seizures. The current article will review all aspects of the discovery, genetics, distribution, pharmacology and function of the 5-ht(6)receptor. Taken together, this wealth of information warrants the use of the upper case nomenclature for the 5-ht(6) receptor to be approved and its true status recognised.
 ...
PMID:5-ht6 receptors. 1496 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>