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)

A case of fluoxetine toxicity in a newborn of 38 weeks' gestation has been presented. The total drug concentration in cord blood was 80 ng/mL. The fluoxetine level, 26 ng/mL, is below the adult therapeutic level; the norfluoxetine cord blood level, 54 ng/mL, is at the adult therapeutic level. At 96 hours the fluoxetine level was not measurable and the norfluoxetine level was 55 ng/mL. The parent compound is fluoxetine, which is metabolized in the liver to norfluoxetine. The half-life of fluoxetine is 2 to 3 days, and that of norfluoxetine is 7 to 9 days. Interestingly, in our patient the fluoxetine was absent in the blood at 4 days, but norfluoxetine was present. The most common side effects of Prozac in adult patients involve primarily the central nervous system and include nervousness, tremor, jitteriness, and occasionally seizures. Central nervous system symptoms were most prominent in this newborn. He also had an increased heart rate. Cardiovascular side effects are less prominent in adults who are taking Prozac. The neonate in this case was asymptomatic at 96 hours of age, indicating that the parent compound, fluoxetine, may be the active part of the drug and side effects may be caused by the parent compound.
 ...
PMID:Fluoxetine hydrochloride (Prozac) toxicity in a neonate. 841 64

Fluoxetine, a serotonin (5-HT) reuptake inhibitor, has been documented to exert a protective action against convulsive seizures in animal models, when administered either systemically, or focally into substantia nigra. It is likely that the mechanism of anticonvulsant action of fluoxetine is due to an enhancement of endogenous 5-HT transmission. To evaluate this possibility in the context of the anticonvulsant action of intranigral fluoxetine, we examined the influence of 5-HT-mediated transmission in substantia nigra on seizure susceptibility in a rat model of focally evoked complex partial seizures. In addition to fluoxetine (3.5 nmol), we found that the directly acting 5-HT receptor agonists, 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (10 nmol), 1-(3-chlorophenyl)piperazine (m-CPP) (7.4 nmol), gepirone (70 nmol) and 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) (10 nmol), when microinjected bilaterally into substantia nigra, protected rats from limbic motor seizures evoked focally from area tempestas, an epileptogenic site in the deep rostral piriform cortex. This indicates that multiple 5-HT receptor subtypes in substantia nigra may contribute to seizure regulation. Consistent with this, the 5-HT antagonist, metergoline, partially reversed the anticonvulsant action of intranigral fluoxetine. Depletion of endogenous 5-HT, by pretreatment with parachlorophenylalanine (PCPA), completely prevented the anticonvulsant action of intranigral fluoxetine, without modifying the anticonvulsant effect of intranigral TFMPP. These findings support the proposal that the anticonvulsant action of fluoxetine in substantia nigra is due to an enhancement of the synaptic action of endogenous 5-HT in substantia nigra which in turn is mediated via multiple 5-HT receptors. Endogenous 5-HT transmission in substantia nigra is therefore capable of limiting the development and propagation of seizure activity generated in limbic circuits.
 ...
PMID:The anticonvulsant action of fluoxetine in substantia nigra is dependent upon endogenous serotonin. 881 59

Fluoxetine, an antidepressant which is used world-wide, is a prominent member of the class of selective serotonin re-uptake inhibitors. Recently, inhibition of voltage-gated Na(+) and K(+) channels by fluoxetine has also been reported. We examined the effect of fluoxetine on voltage-gated calcium channels using the patch-clamp technique in the whole-cell configuration. In hippocampal pyramidal cells, fluoxetine inhibited the low-voltage-activated (T-type) calcium current with an IC(50) of 6.8 microM. Fluoxetine decreased the high-voltage-activated (HVA) calcium current with an IC(50) between 1 and 2 microM. Nifedipine and omega-conotoxin GVIA inhibited the HVA current by 24% and 43%, respectively. Fluoxetine (3 microM), applied in addition to nifedipine or omega-conotoxin, further reduced the current. When fluoxetine (3 microM) was applied first neither nifedipine nor omega-conotoxin attenuated the remaining component of the HVA current. This observation indicates that fluoxetine inhibits both L- and N-type currents. In addition, fluoxetine inhibited the HVA calcium current in carotid body type I chemoreceptor cells and pyramidal neurons prepared from prefrontal cortex. In hippocampal pyramidal cells high K(+)-induced seizure-like activity was inhibited by 1 microM fluoxetine; the mean burst duration was shortened by an average of 44%. These results provide evidence for inhibition of T-, N- and L-type voltage-gated calcium channels by fluoxetine at therapeutically relevant concentrations.
 ...
PMID:Inhibition of voltage-gated calcium channels by fluoxetine in rat hippocampal pyramidal cells. 1072 13

A one-year-old, neutered female Skye terrier presented with anorexia, vomiting, seizures and ascites. Portal venography demonstrated the presence of multiple acquired portosystemic shunts. Hepatic biopsy confirmed the presence of copper accumulation and fibrosis. Treatment included ursodeoxycholic acid therapy, colchicine and oral zinc. To the authors' knowledge, this is the first case report detailing successful management of Skye terrier hepatopathy.
 ...
PMID:Diagnosis and management of hepatic copper accumulation in a Skye terrier. 1262 74

The present study was designed to investigate the effects of fluoxetine, a selective serotonin reuptake inhibitor, on ethanol withdrawal syndrome in rats. Adult male Wistar rats (218-255 g) were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Fluoxetine (2.5, 5 and 10 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes and tremor were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. Fluoxetine produced some dose-dependent and significant inhibitory effects on all the signs of ethanol withdrawal during ethanol withdrawal period. Our results suggest that acute fluoxetine treatment has some beneficial effects on ethanol withdrawal in rats. Thus, this drug may be useful for treatment of ethanol withdrawal syndrome.
 ...
PMID:Effects of fluoxetine on ethanol withdrawal syndrome in rats. 1520 97

Fluoxetine, a selective serotonin reuptake inhibitor, is known to increase the cortical content of allopregnanolone (ALLO) without altering the level of other neurosteroids. In contrast to the proconvulsant effect of many antidepressants, fluoxetine exhibits anticonvulsant effects. The present study was undertaken to examine the role of ALLO in the anticonvulsant action of fluoxetine against pentylenetetrazole (PTZ)-induced seizures in mice. Prior administration of GABA(A) receptor agonist muscimol or neurosteroid ALLO or progesterone, a precursor of ALLO or neurosteroidogenic drugs like FGIN 1-27, an agonist at the mitochondrial diazepam binding inhibitor receptor (MDR) or metyrapone, an 11beta-hydroxylase inhibitor, significantly potentiated the anticonvulsant effect of fluoxetine. In contrast, the effect of fluoxetine was counteracted by inhibition of the neurosteroid biosynthesis using drugs like 5alpha-reductase inhibitor, finasteride; 3beta-hydroxysteroid dehydrogenase inhibitor, trilostane; 3alpha-hydroxysteroid dehydrogenase inhibitor, indomethacin; MDR antagonist, PK 11195; or the GABA(A) receptor antagonist, bicuculline. Further, bilateral adrenalectomy had no significant effect on the anticonvulsant action of fluoxetine, suggesting negligible contribution from peripheral steroidogenesis. The anticonvulsant effect of fluoxetine was partially abolished in 5,7-DHT treated mice, indicating that the effect may also, in part, be dependent on serotonergic transmission. Thus, our data indicate that increased synthesis of ALLO in CNS is a major factor that ultimately leads to anticonvulsant effects of fluoxetine against PTZ-induced seizures.
 ...
PMID:Essentiality of central GABAergic neuroactive steroid allopregnanolone for anticonvulsant action of fluoxetine against pentylenetetrazole-induced seizures in mice. 1536 24

G protein-activated inwardly rectifying K+ (GIRK, Kir3) channels play an important role in the inhibitory regulation of neuronal excitability in most brain regions and heart rate through activation of various G protein-coupled receptors, such as opioid, cannabinoid, and D2 dopamine receptors. Therefore, modulators of GIRK channels may affect many brain functions. We have shown using Xenopus oocyte expression assays that ethanol directly activates GIRK channels, whereas various antipsychotics (thioridazine, clozapine, pimozide, and haloperidol) inhibit the channels. Here we investigated not only the effects of various selective serotonin reuptake inhibitor (SSRI) antidepressants (fluoxetine, citalopram, fluvoxamine, and zimelidine) and risperidone, an atypical antipsychotic, on GIRK channels, but also those of the various drugs tested on other Kir channels using the Xenopus oocyte system. Fluoxetine inhibited GIRK channels, whereas the other SSRIs and risperidone had a small or no effect on the channels. In contrast, Kir1.1 and Kir2.1 channels were insensitive to ethanol and various SSRIs and antipsychotics, although thioridazine weakly inhibited Kir1.1 channels. It has been shown that the function of GIRK channels is involved in seizure susceptibility, antinociception by opioids, cannabinoids, or ethanol, and cocaine reinforcement in studies using GIRK knockout mice and weaver mutant mice that have mutant GIRK2 channels insensitive to G proteins and ethanol. Activation of GIRK channels by opioids, cannabinoids, or ethanol may be one of these key effects. Therefore, GIRK channel modulators might be potential agents for the treatment of users of addictive drugs, such as cocaine, opioids, cannabinoids, and ethanol, as well as for the treatment of epilepsy and pain.
 ...
PMID:Modulators of G protein-activated inwardly rectifying K+ channels: potentially therapeutic agents for addictive drug users. 1554 67

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.
 ...
PMID:Effect of anxiolytic, antidepressant, and antipsychotic drugs on cocaine-induced seizures and mortality. 1558 32

The effects of tianeptine and fluoxetine on pentylenetetrazole (PTZ)-induced seizures in rats were investigated. Female Wistar rats (172-278 g) were used in the study. Tianeptine (1.25, 2.5, 5, 10 and 20 mg/kg) and fluoxetine (2.5, 5, 10 and 20 mg/kg) or saline were injected to rats intraperitoneally 30 min before PTZ (50 mg/kg) injections. Immediately after PTZ administrations, latency and intensity of the PTZ-induced seizures was recorded and scored, respectively. Fluoxetine (2.5-20 mg/kg) did not produce any significant difference in latency and intensity of the PTZ-induced seizures. Although tianeptine (1.25-20 mg/kg) also did not affect the latency time, it produced significant attenuations in the intensity of the seizures. Tianeptine did not cause any significant change in the locomotor activity of the rats. The results of this preliminary study suggest that tianeptine but not fluoxetine has some inhibitory effects on PTZ-induced seizures in rats.
 ...
PMID:Investigation of the effects of tianeptine and fluoxetine on pentylenetetrazole-induced seizures in rats. 1558 68

The aim of this study was to examine the effects of acute fluoxetine treatment on pentylenetetrazol-induced convulsions in order to shape a model of seizures associated with treatment with antidepressants in rats. Moreover, the putative role of the hippocampal formation in this respect was investigated with the help of c-fos immuncytochemistry to mark local neuronal activity. It was found that fluoxetine (10.0 mg/kg, i.p.) enhanced the proconvulsive effect of pentylenetetrazol (50.0 mg/kg, i.p.), and simultaneously inhibited pentylenetetrazol-stimulated c-Fos expression in some areas of the hippocampus. Fluoxetine pretreatment did not alter pentylenetetrazol brain concentration indicating that this phenomenon was not related to the pharmacokinetic interaction. It is suggested that inhibition by fluoxetine of some neuronal populations contributing to the local feedback mechanism controlling excessive epileptiform discharges within the hippocampus might lead to an increase in epileptic activity. The reported in the present paper fluoxetine versus pentylenetetrazol interaction may, therefore, serve as a model of seizures associated with treatment with antidepressants.
 ...
PMID:The effect of fluoxetine in a model of chemically induced seizures--behavioral and immunocytochemical study. 1561 48


<< Previous 1 2 3 4 Next >>