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)

The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. 183 Nov 22

MK-801 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant and neuroprotective properties. The action of MK-801 (0.05-10 mg/kg IP) was assessed against pentylenetetrazol-induced seizures (PTZ; 100 mg/kg SC; 30 min after MK-801) in rats aged 7, 12, 18, 25, and 90 days (N = 263). We observed pronounced ataxia and hypermobility after MK-801 pretreatment during the whole ontogenesis, and the animals exhibited head-weaving and body-rolls. After the combination of MK-801 and PTZ "wet dog shakes" were detected in 18-, 25-, and 90-day-old rats (never seen in controls receiving PTZ only). MK-801 only insignificantly modified the latencies of minimal (clonic) seizures in 18-day-old and older rats where this seizure type is regularly elicited. In 12-day-old rats an increased incidence of minimal seizures was detected. MK-801 nearly completely blocked or strongly delayed major (generalized tonic-clonic) seizures and attenuated the seizure severity during ontogenesis in a dose-dependent manner. Present results suggest the important role of NMDA receptors in the genesis of generalized tonic-clonic seizures whilst the role of NMDA receptors in minimal seizures appears to be negligible during the whole ontogenetic development.
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PMID:Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. II. The effects of MK-801. 183 2

AHR-12245, 2-(4-chlorophenyl)-3H-imadazo[4,5-b]pyridine-3-acetamid, ethosuximide, Na valproate, phenytoin, and clonazepam were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that the anticonvulsant profile of AHR-12245 is similar to that for ethosuximide and clonazepam. AHR-12245 is effective in nontoxic intraperitoneal doses in mice by the maximal electroshock seizure (MES), pentylenetatrazol (s.c. PTZ), bicuculline, and picrotoxin tests but ineffective against strychnine-induced seizures; it is effective after nontoxic oral doses in both mice and rats by the s.c. PTZ test and ineffective by the MES test. The candidate antiepileptic substance was also ineffective against seizures induced in amygdala and corneally kindled rats. The PIs for AHR-12245 by the s.c. PTZ test were 4.5 to 12 times higher than those for the prototype agents, except that for clonazepam when administered orally in mice. The in vitro studies indicate that AHR-12245 is a weak inhibitor of benzodiazepine (BDZ) receptor binding but does inhibit adenosine uptake. These results indicate that AHR-12245 is a relatively nontoxic agent with a profile of anticonvulsant action which suggests it should be useful in generalized absence seizures.
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PMID:AHR-12245: a potential anti-absence drug. 190 25

Evaluation of patients with syncope often includes a battery of noninvasive tests. In this study, 45 patients (26 with suspected neurologic and 19 with suspected cardiac syncope) were evaluated with simultaneous 24-hour electroencephalographic (EEG) and 2-channel electrocardiographic (ECG) recordings. Isolated cardiac rhythm abnormalities were noted in 21 patients, but none of these was symptomatic and no definitive arrhythmias occurred. Isolated EEG abnormalities were noted in 11 patients, 5 of whom had EEG abnormalities consistent with seizure disorders. Simultaneous EEG and ECG abnormalities were seen in 4 patients. In 2 cases, a previously unsuspected etiology for syncope was found: seizures in 1 patient with heart disease, and sinus pauses in another thought to have a seizure disorder. Thus, combined ambulatory EEG/ECG monitoring may prove useful in the evaluation of some patients with syncope.
Am J Cardiol 1991 Oct 15
PMID:Combined ambulatory electroencephalographic and electrocardiographic recordings for evaluation of syncope. 192 21

Abecarnil (ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboxylate) is a metabolically stable beta-carboline derivative with potent anxiolytic and few sedative and ataxic effects in rodents. The anticonvulsant and muscle relaxant actions of abecarnil have been evaluated in mice, rats, gerbils and baboons. Abecarnil raised the threshold for tonic electroconvulsions in mice after corneal but not after auricular application, had no effect on maximal electroshock-induced tonic convulsions triggered by either method, protected mice against the tonic hindlimb extension in PTZ-, picrotoxin- and 3-mercaptopropionate-induced seizures and blocked clonus after PTZ, DMCM (methyl-4-ethyl-6,7-dimethoxy-9H-pyrido-(3,4-b)-indol-3-carboxylate) and 3-mercaptopropionate. Abecarnil had no effect on convulsions induced by bicuculline and strychnine. Furthermore, abecarnil blocked kindled seizures after chronic administration of PTZ and FG 7142 (beta-carboline-3-carboxylic acid methylamide) and protected mice and rats against limbic convulsions induced by pilocarpine. Severity and afterdischarge duration of amygdala-kindled seizures were reduced in rats treated with abecarnil. Abecarnil also antagonized selectively convulsions induced by i.c.v. administration of kainate, but not those triggered by N-methyl-D-aspartate or quisqualate. In genetic models of reflex epilepsy, abecarnil was effective against sound-induced convulsions in DBA/2 mice, against air blast-induced generalized seizures in gerbils and against myoclonus in baboons Papio papio. The anticonvulsant effect of abecornil in a PTZ seizure model in mice was potentiated by ethosuximide, whereas no significant potentiation was found with diazepam, clonazepam, diphenylhydantoin, carbamazepine and phenobarbital. Electromyographic monitoring in a etorphine model of muscle rigidity in rats showed no or little muscle relaxant effect of abecarnil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant action of the beta-carboline abecarnil: studies in rodents and baboon, Papio papio. 197 Mar 62

This study evaluates the glycine potentiation of anticonvulsant drugs in subcutaneous pentylenetetrazol seizures in rats. Administered alone, glycine (30 or 40 mM/kg, PO) induced no anticonvulsant effect or neurological deficit. Coadministered with anticonvulsants, glycine significantly enhanced the anticonvulsant potency of diazepam and sodium valproate without affecting the neurological deficit induced by the anticonvulsants. Glycine did not significantly alter the anticonvulsant activity of ethosuximide or phenobarbital. These findings indicate a possible glycine-sensitive component in the mechanism of action of diazepam and sodium divalproate in subcutaneous pentylenetetrazol seizures. With the possible exception of sodium valproate, the present study provides little support for a glycine and gamma-aminobutyric acid (GABA) interaction as a mechanism of anticonvulsant activity in SC PTZ seizures. Further studies are required to determine the role of strychnine-sensitive and strychnine-insensitive glycine receptors in this experimental model of absence epilepsy.
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PMID:Glycine potentiation of anticonvulsant drugs in pentylenetetrazol seizures in rats. 201 17

We have cloned NGFI-C, a nerve growth factor-induced early-response gene which encodes a Cys2/His2 zinc finger protein. RNA blot analysis demonstrates that NGFI-C mRNA is induced within minutes of stimulation of PC12 cells by nerve growth factor and is similarly activated in brain after a Metrazol-induced seizure. The cDNA sequence predicts a protein that contains three zinc fingers which show striking homology to the DNA-binding regions of three previously reported zinc finger proteins, NGFI-A, Krox-20, and the Wilms' tumor gene product. NGFI-C binds to the previously described DNA-binding site of these three proteins, which is GCGGGGGCG. Cotransfection experiments revealed that NGFI-C strongly activates transcription from this site in mammalian cells. The isolation of another early-response gene that encodes a member of the G(C/G)G or GSG element-binding family should provide an opportunity to investigate the relative contributions of a family of transcription factors to the cell's response to changes in its environment.
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PMID:The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family. 207 95

Inbred mouse strains differed significantly in sensitivity to convulsions induced by 9 convulsant drugs administered using a timed infusion procedure. Some strains (e.g. BALB/cJ, A/J) were generally seizure-susceptible, while some were generally seizure resistant (e.g. C57BL/6J, SWR/J). However, the overall pattern of strain sensitivities was complex, and depended upon drug and convulsant sign. Five of the drugs (bicuculline, DMCM, picrotoxin, TBPS and pentylenetetrazol (PTZ] produce convulsions, at least in part, through their interactions with the GABA receptor, while the other 4 (strychnine, CHEB, 4-aminopyridine and kainic acid) act through independent mechanisms. We predicted that responses to drugs with similar mechanisms of action would be genetically correlated. However, strains sensitive to picrotoxin-induced convulsions were not necessarily sensitive to convulsions elicited by PTZ or TBPS. Furthermore, different convulsant signs produced by a single drug were not always strongly correlated. Instead, genetic correlations were found among inbred strains for sensitivity to similar convulsant signs produced by different drugs. This suggests that genetic variation in sensitivity to these convulsant drugs arises primarily from variation in systems important for the expression of the convulsion.
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PMID:Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs. 207 20

Generalized tonic-clonic seizures are a neurologic emergency. Duration of ictal activity has been associated with neurologic sequelae. The purpose of this study was to determine if midazolam, a short-acting benzodiazepine, could effectively ablate ictal activity in an animal model without significant cardiorespiratory compromise. Ten domestic swine (10 to 20 kg) were ventilated and hemodynamically monitored. Bifrontal craniotomies were performed and electrocortical activity was recorded throughout the experiment. Pentylenetetrazol (100 mg/kg) was administered iv to induce seizures. Midazolam (0.1 mg/kg) was administered iv and serum levels were drawn at 1, 2, 5, 10, 15, and 20 min after administration. There was no significant difference between the baseline and postmidazolam vital signs. Seizure activity was seen periodically as generalized spikes, as well as individual spikes for 29 +/- 5 sec after midazolam administration. A period of attenuation of 24 +/- 7 sec was seen before returning to baseline electrocortical activity. Our study demonstrates that midazolam effectively ablated induced ictal activity without significant cardiorespiratory depression and with similar EEG effect as other benzodiazepines.
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PMID:Intravenous midazolam suppression of pentylenetetrazol-induced epileptogenic activity in a porcine model. 210 74

The anticonvulsant action of 2-amino-7-phosphonoheptanoate (AP7) was assessed during ontogenesis of the rat. Animals of five age groups (7, 12, 18, 25, and 90 days) were pretreated with AP7 i.p. in the doses from 15 to 60 mg/kg 30 min prior to pentamethylenetetrazol (PTZ; metrazol; 100 mg/kg s.c.). The incidence and latency of minimal seizures (pure clonic without the loss of righting ability) and of generalized tonic-clonic seizures (major) were evaluated and compared with the control groups. Minimal metrazol seizures were not regularly observed in controls between ages 7 and 12 days. An increased incidence was noticed in AP7-treated groups. In animals of 18 days of age and older the AP7-pretreatment did not influence incidence of minimal seizures; the latencies were significantly lengthened only in 18-day-old animals. Major seizures were significantly suppressed with the highest dose of AP7 (60 mg/kg) in all groups except 7-day-old rats. In 90-day-old rats all doses of AP7 were effective in the suppression of major seizures. The latencies of major seizures were increased in 7 and 18 days old rats. It appears that the blockade of NMDA receptor substantially influences the major seizures induced by PTZ, whereas minimal (clonic) seizures are affected weakly. This suggests an important role of NMDA receptor-mediated transmission in the genesis of generalized tonic-clonic seizure pattern.
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PMID:Excitatory amino acid antagonists and pentylenetetrazol-induced seizures during ontogenesis. I. The effects of 2-amino-7-phosphonoheptanoate. 216 Oct 66


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