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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of atropine or diazepam pretreatment on soman-induced convulsions and brain phosphoinositide (PI) metabolism, as assessed by brain regional inositol-1-phosphate (IP1) levels, were studied in saline and LiCl-pretreated rats. IP1, an intermediate in PI turnover, was measured in cortex, caudate, thalamus, hippocampus, and cerebellum. Soman (100 micrograms/kg; sc) produced convulsions in 63% of the saline-pretreated rats, whereas with LiCl pretreatment all rats exposed to 100 micrograms/kg of soman had tonic-clonic convulsions. Thus, LiCl pretreatment potentiated soman-induced convulsions. Tissue IP1 increased severalfold in soman-exposed convulsing rats with the highest increases being in frontal cortex and caudate. In contrast, no marked increases of IP1 occurred in similarly treated nonconvulsing rats. LiCl treatment itself increased IP1 levels without causing convulsions. In LiCl-pretreated rats, soman again markedly elevated IP1 levels above LiCl alone in convulsing rats, whereas no such effect occurred in nonconvulsing rats. In LiCl-pretreated rats, the increased IP1 levels associated with soman-induced convulsions were greatest in hippocampus and piriform cortex. Thus, LiCl appears to lower the threshold for the spread of seizure activity through limbic structures, thereby potentiating cholinergic-induced convulsions. Diazepam and atropine both blocked soman-induced convulsions, and brain regional IP1 elevations were concomitantly abolished as well. These results indicate that soman-induced convulsions involve the inositol lipid signaling system. This involvement is potentiated by lithium but attenuated by atropine and diazepam.
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PMID:Soman-induced convulsions affect the inositol lipid signaling system: potentiation by lithium; attenuation by atropine and diazepam. 284 36

Studies suggest that the 1,5-benzodiazepine clobazam possesses a favorable anticonvulsant profile due to its minimal neurotoxicity. The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone. All drugs produced a significant, dose-dependent decrease in the duration of both behavioral and electrographic kindled seizure measures. Forelimb clonus suppression was the most sensitive measure of anticonvulsant drug effect. The order of potency for all effects was clonazepam greater than diazepam greater than clobazam. ED50s for the benzodiazepines' effects on motor impairment were compared to their ability to protect rats from forelimb clonus. Different spectrums of action for the various benzodiazepines were found depending on the comparison measure. Clonazepam had the most favorable ratio of potency for anticonvulsant vs. motor impairment activity when ataxia rating was the comparison measure. Diazepam had the most advantageous profile when the more sensitive screen test was used for comparison. Clobazam was not found to have a superior spectrum of action when compared across these measures. The results emphasize the importance of dose-response analyses and the consideration of behavioral measures used to assess beneficial and adverse effects of anticonvulsants.
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PMID:A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function. 291 46

The anticonvulsive action of diazepam, carbamazepine, sodium valproate and their combinations with pyridoxal-5-phosphate, nicotinamide, and alpha-tocopherol were investigated in acute experiments on mice with corazole-induced seizures. Diazepam (0.5 mg/kg), carbamazepine (50 mg/kg) and sodium valproate (200 mg/kg) were shown to reduce convulsive intensity and lethality. Vitamins nicotinamide (250 mg/kg), pyridoxal-5-phosphate (10 mg/kg) and alpha-tocopherol (100 mg/kg) potentiated anticonvulsive action of the above antiepileptic drugs. The results of the investigation suggest the efficacy of pathogenetic therapy and give new evidence of the advisability of using vitamins in combination with synthetic anticonvulsive drugs.
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PMID:[Effect of diazepam, carbamazepine, sodium valproate and their combinations with vitamin preparations on epileptic activity]. 293 95

The prophylactic effect of an inhibitor of synaptosomal GABA uptake, SK&F 89976-A (N-[4,4-diphenyl-3-butenyl]-nipecotic acid), on the development of amygdala kindled seizures was studied in adult female rats. For comparative purposes, the action of diazepam was also investigated. Dosages of SK&F 89976-A and diazepam which were previously shown to be the ED50 for seizure inhibition in fully kindled rats (15 mg/kg and 2 mg/kg i.p., respectively) were administered daily 30 min prior to amygdala stimulation in naive, unkindled rats. Both drugs inhibited the evolution of full kindled seizure activity and markedly suppressed kindling-associated increases in the duration of behavioral and electrographic seizures. Control rats developed fully kindled stage 5 seizures after 8.9 +/- 1.1 amygdala stimulations but drug-treated rats did not progress beyond an early stage of kindled seizures as long as the animals were treated with the drugs (22 days). Diazepam produced significant CNS depressant effects throughout the course of administration but SK&F 89976-A prevented kindling with no depressant side effects. The ability of SK&F 89976-A and diazepam to inhibit the development of full amygdala kindled seizures may be related to enhancement of central inhibitory GABAergic systems.
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PMID:Prophylaxis of amygdala kindling-induced epileptogenesis: comparison of a GABA uptake inhibitor and diazepam. 297 79

Wistar rats in our laboratory breeding colony spontaneously present petit mal-like, non-convulsive, epileptic seizures. In these rats, as in other animal petit mal models, GABAmimetics, agonists of GABA-A receptors such as 4, 5, 6, 7 tetrahydroisooxazolo (5,4-c) pyridin-3-ol (THIP), or inhibitors of GABA catabolism such as gamma-vinyl GABA (GVG) or L-cycloserine (CYC), aggravated the seizures. Diazepam not only abolished the spontaneous seizures but also completely blocked the effects of the GABAmimetics, totally suppressing seizures in rats given THIP, GVG or CYC. These findings show that the mode of action of benzodiazepines is not comparable to a non-specific potentiation of GABA transmission, and suggest that the anti-absence effects of the benzodiazepines could depend on interactions with neurotransmitter systems other than GABA.
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PMID:Diazepam antagonizes GABAmimetics in rats with spontaneous petit mal-like epilepsy. 299 58

Rats implanted with amygdaloid stimulating and cortical recording electrodes were kindled by daily low-intensity electrical stimulation. In one experiment amino acid concentrations were measured in amygdala, cortex and hippocampus at behavioural stages 1, 2 and 4 (Racine). Control groups consisted of unstimulated rats. Only alanine showed a significant enhancement of concentration in the kindled rats (stage 4 of Racine). In a second experiment, a group of rats was treated daily with 10mg/kg p.o. of diazepam. Diazepam significantly inhibited kindling and no changes in amino acid concentrations were observed in this group. Increased alanine levels are seen after various seizure types; since pentetrazole, isoniazid and beta-vinyllactic acid seizures were associated with alanine level increases only after and never before seizure occurrence, it is suggested that the alanine increases are a consequence rather than a cause of convulsions. In 3H-flunitrazepam binding studies, no change in affinity or receptor number could be demonstrated during kindling.
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PMID:Pharmacological and neurochemical aspects of kindling. 299 74

The action of opiate receptor agonists: (D-Ala2)-methionine enkephalinamide (D-MEA), morphine, heroin, etorphine, and antagonists: naloxone and diprenorphine on audiogenic seizures was tested during ethanol abstinence. The action of diazepam and clonidine was also tested Morphine (5 and 20 mg/kg), but not heroin and etorphine, given intraperitoneally inhibited the seizures, similarly as intraventricularly administered D-MEA did. However, morphine given by this route was ineffective. Diazepam and clonidine inhibited audiogenic seizures: the action of clonidine was counteracted by yohimbine, but not by prazosin. The results may be considered as supporting the hypothesis on the participation of opioid system in ethanol abstinence. However, the participation of gabergic and noradrenergic systems cannot be ruled out: these systems may possibly interact with the opioid system in evoking the symptoms of ethanol abstinence.
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PMID:Involvement of opioid and other systems in ethanol abstinence audiogenic seizures in the rat? 299 52

Three benzodiazepine (BZ) receptor ligands of the beta-carboline group, namely the BZ receptor agonist ZK 93 423, the partial agonist ZK 91 296, and the antagonist ZK 93 426, were studied in epilepsy-prone Mongolian gerbils with different seizure types. Diazepam and clonazepam were included in these studies for comparison. In vivo binding studies in gerbils showed that all compounds were potent in displacing [3H]lormetazepam from binding sites in cerebellum and forebrain. Except for ZK 93 426, all drugs proved capable of dose dependently protecting gerbils from minor (myoclonic) and major (tonic-clonic) seizures induced by air blast stimulation. For ZK 93 423, ZK 91 296, diazepam and clonazepam, a highly significant correlation was found between anticonvulsant ED50S and ED50S for displacement of [3H]lormetazepam binding. Calculation of receptor occupancy revealed that beta-carbolines and benzodiazepines displayed anticonvulsant effects in gerbils at low occupancy (8-15% in forebrain). Even at almost total receptor occupancy, the BZ receptor antagonist ZK 93 426 was without any effect on seizure behaviour but antagonized the anticonvulsant effect of ZK 91 296. In contrast to diazepam, ZK 91 296 was devoid of any sedative side-effects even at 90% receptor occupancy. The data suggest that anticonvulsant beta-carbolines deserve interest as a new type of anticonvulsant drug.
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PMID:Evaluation of different beta-carbolines in Mongolian gerbils with reflex epilepsy. 299 8

The effects of selected modulators of GABAergic transmission, either alone or in combination, were tested for their potency on the seizure pattern and mortality induced by convulsant drugs in rat. Pentobarbital and diazepam were effective against both tonic and clonic seizure components induced by bicuculline and picrotoxin. The anticonvulsant profile of ethanol closely resembled that of pentobarbital. Pentobarbital, diazepam and ethanol did not modify seizures induced by strychnine. In contrast, progabide, a central gamma-aminobutyric acid (GABA) receptor agonist, caused significant protection only against convulsions induced by strychnine and its lethality, but did not protect against seizures induced by bicuculline or picrotoxin. Data on interaction of drugs with subprotective doses of these agents clearly demonstrated potentiation of the anticonvulsant actions of these modulators. Thus, seizures induced by bicuculline were more sensitive to the inhibition by pentobarbital in combination with diazepam or ethanol, while pentobarbital with progabide was equally effective against convulsions induced by GABA antagonists. Diazepam, in combination with progabide, blocked only convulsions induced by picrotoxin. Ethanol, in combination with either pentobarbital or with diazepam, was effective against all the three convulsant drugs. These results are consistent with the concept that drugs which facilitate GABAergic transmission are effective against seizures related to an impairment of GABA transmission. Further, the present data indicate that tonic seizures are more susceptible to the actions of drugs than the clonic component. Smaller doses of these drugs, alone or in combination, modified the seizure patterns and mortality, whereas at larger doses, the possible involvement of a nonspecific depressant action cannot be ruled out.
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PMID:Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism. 301 Jan 61

Dibutyryl cyclic GMP (DbcGMP) or dibutyryl cyclic AMP (DbcAMP) given to rats intracerebellarly in a dose of 200 nmol/head produced electroencephalographic convulsive changes. Intracerebellar (i.c.) administration of lower doses (100 nmol/head) of DbcGMP and DbcAMP and 200 nmol/head of norepinephrine (NE) and glutamate (Glu) facilitated the pentylenetetrazol (PTZ)-induced convulsions. Diazepam (100 nmol/head, i.c.) suppressed the PTZ-induced convulsions. GABA (400 nmol/head, i.c.) did not affect the PTZ-induced convulsions. These results suggest that DbcGMP, DbcAMP and Glu inhibit seizure control mechanisms in the cerebellum, and that one of the sites of the anticonvulsant action of diazepam is located in the cerebellum.
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PMID:Cerebellar cyclic nucleotides and the development of convulsion, with reference to the anticonvulsant activity of diazepam. 301 17


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