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

The antagonism of various components of maximal Metrazol-seizures (MMS) (i.e. tonic hindpaw extension, tonic backward extension of the forepaws, generalized clonic seizures and tremors), ataxia and loss of righting reflex-activity have been studied in a standardized procedure comparing 41 antiepileptics and related compounds. Appropriate analyses (Cluster Analysis and Principal Component Analysis) resulted in the distinction of seven clusters which could be considered along two continua. A first continuum is characterized by a progressive strengthening of loss of righting reflex-inducing properties, a decreasing dissociation of ataxia and loss of righting reflex and the disappearance of a selective anticonvulsant effect. The second continuum is characterized by an increasing relative potency of ataxia-inducing properties, an increasing dissociation of ataxia and loss of righting reflex and a decreasing antagonism of tremors. Three main types of anticonvulsants could be defined: drugs with a complete anti-MMS effect antagonizing both clonic and tonic seizures; drugs selectively abolishing tonic seizures, i.e., tonic extension of hind- and forepaws; and drugs exclusively blocking tonic hind-paw extension. The neurological and clinical significance of these different types of anticonvulsant activity has been discussed. Finally, the described modification of the maximal Metrazol-seizures test is proposed for routine screening purposes.
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PMID:Antagonism of maximal metrazol seizures in rats and its relevance to an experimental classification of antiepileptic drugs. 103 60

Changes in cardiodynamics and regional blood flow were examined in chronically prepared paralyzed cats during seizures induced electrically by transcerebral or direct cortical stimulation or by administration of flurothyl ether (Indoklon) or pentylenetetrazol (Metrazol). Transcerebral and chemical stimuli produced the greatest vascular responses. During seizures there was an abrupt elevation of arterial pressure unassociated with consistent changes in heart rate. Vascular resistance was increased in femoral, renal and mesenteric arteries with variable reductions in blood flow. Resistance was decreased and flow passively increased in the common carotid artery reflecting the loss of cerebral autoregulation. Cardiac output was unchanged. With seizures associated with large elevations of arterial pressure, the central venous and left ventricular end-diastolic pressures were markedly increased indicating incipient congestive failure. The pressor response was blocked by alpha-adrenergic blockade with phentolamine. Increased regional vascular resistance was abolished by regional sympathectomy. While either adrenalectomy or treatment with 6-hydroxydopamine alone failed to abolish the pressor response, combined, they did. Such treatment unmasked an atropine-sensitive bradycardia. The pressor response with seizures is a consequence of increased vascular resistance in viscera and muscles due to widespread activation of sympathetic neurons and release of adrenomedullary catecholamines. Co-activation of cardiovagal and cardiosympathetic neurons may underlie some associated arrhythmias. Cardiovascular events may severe, by redistribution of the cardiac output, to assure increased availability of oxygen and nutrients to brain to meet the metabolic demands of convulsions.
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PMID:Changes in regional blood flow and cardiodynamics associated with electrically and chemically induced epilepsy in cat. 113 82

Reserpine analogues obtained from strip-down parts of the parent molecule were studied for their effects on experimental convulsive seizures and amphetamine antagonism. The unsubstituted and M-methoxy substituted piperidino- and morpholino acetanilides derived from A, B and C rings or reserpine showed prominent anticonvulsant activity as against the known lowering of threshold activity by reserpine. Methoxy morpholino derivative showed prominent activity with least sedative effect. gamma-Piperidino acetanilide showed a dual effect such that at higher doses it itself produced clocin covulsions. The effects were non-specific since they unpreferentially antagonized the maximal electrochock, Metrazol and strychnine convulsions Compounds derived from C, D and E rings of reserpine did not significantly increase or decrease the seizure thresholds.
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PMID:Pharmacological actions of some simple analogues of reserpine. II. Anticonvulsant effects. 116 75

A patient with an acute anterior wall myocardial infarction complicated by bilateral bundle branch block and paroxysmal AV block is presented. The following new, uncommon or unreported phenomena were documented: the simultaneous occurrence of phase-3 block in the right bundle branch and phase-4 block in the left bundle branch; the simultaneous occurrence of phase-4 block in both main bundle branches; phase-4 left posterior hemiblock associated with escape beats arising from the injured posterior division of the left bundle branch; supernormal conduction in the right bundle branck and 2:1 right bundle branch block related to supernormality. Most of these changes were, of course, not simultaneous, and their successive appearance was related to day-to-day and sometimes hour-to-hour variations in the degree and quality of the multifascicular injury caused by the infarct. In addition, the actions of several drugs upon automaticity and conduction were tested. The effects of amiodarone, lidocaine and isoproterenol were similar to those previously reported under comparable circumstances. At a moment when the patient had repeated episodes of paroxysmal AV block with severe Adams-Stokes seizures, the administration of a single i.v. dose of 0.25 mg of strophanthin suppressed totally the Adams-Stokes attacks through a significant enhancement of ventricular automaticity. If rapid implantation of an artifical pacemaker is not at hand, strophanthin may be life-saving in patients with acute paroxysmal AV block.
Eur J Cardiol 1975 Dec
PMID:Electrophysiologic and pharmacologic studies in a patient with acute myocardial infarction complicated by intraventricular and atrioventricular block. 119 12

The anticonvulsant activity of delta9-tetrahydrocannabinol (delta9-THC) has been determined against seizures induced in epileptic chickens by intermittent photic stimulation (IPS) and in epileptic and nonepileptic chickens by Metrazol. Intravenous administration of the drug reduced both the severity and incidence of seizures evoked by IPS in epileptic chickens. This anticonvulsant action was accompanied by a reduction in frequency of inter-ictal slow-wave high-voltage electroencephalographic activity and by the absence of spiking during IPS. delta9-THC did not affect the incidence of Metrazol-induced seizures in epileptic or nonepileptic chickens.
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PMID:Epileptiform seizures in domestic fowl. V. The anticonvulsant activity of delta9-tetrahydrocannabinol. 122 70

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.
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PMID:Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. 127 53

The convulsant profile of lindane was investigated in OF1 and NMRI mice lines in relation to other convulsants acting at the GABAA and NMDA receptor complexes. Thus, a specific GABA-gated chloride channel blocker, PTX, a GABAA receptor antagonist, PTZ, and an excitatory amino acid receptor agonist, NMDA, were used. Antagonism of the convulsant effects of each of these drugs was investigated with (+)MK-801, a blocker of the NMDA-operated cation channel, and with nifedipine, a voltage-dependent calcium channel antagonist. While no differences in potency for PTX or PTZ to induce seizures were observed between OF1 and NMRI mice, lindane was approximately 80 and 90% more potent in its ability to induce seizures and lethality, respectively, in OF1 than in NMRI mice. Brain lindane concentrations at the moment of convulsion, measured after ED100 doses of lindane (400 and 200 mg/kg for NMRI and OF1 mice, respectively), did not differ between OF1 and NMRI mice, suggesting that the different potency of lindane between these mouse lines is a consequence of pharmacokinetic factors. Furthermore, (+)MK-801 antagonized seizures induced by either lindane, PTX or PTZ with similar potencies in both mouse lines. These results, coupled with the different pharmacokinetics of lindane in OF1 and NMRI mice, suggest that the distinct effects of lindane in these mice are not mediated by different activities at either NMDA or GABAA receptor complexes. Nonetheless, nifedipine antagonized lindane-induced seizures with a three-fold higher potency in NMRI than in OF1 mice. In contrast, nifedipine failed to antagonize PTX and PTZ convulsions in both OF1 and NMRI mice. These results suggest that besides the GABAA receptor complex other mechanisms related to calcium mobilization may be involved in the convulsant action of lindane.
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PMID:Lindane-induced convulsions in NMRI and OF1 mice: antagonism with (+)MK-801 and voltage-dependent calcium channel blockers. 128 May 23

Female rats have a higher threshold than males for seizures induced by the convulsant pentylenetetrazol, a GABAA receptor-chloride channel complex blocker. No sex difference was observed for the anticonvulsant activities of ethanol or diazepam to protect against pentylenetetrazol seizures. Ovariectomy reduces the pentylenetetrazol seizure threshold of females to that of males. In contrast, females have a lower threshold than males to electroshock seizures. Pentylenetetrazol receptors were compared in males and females and gonadectomized animals by binding of several radioligands to the GABAA receptor complex. No differences were found for these four groups of animals in the binding of [3H]flunitrazepam to the benzodiazepine sites and [35S]t-butyl bicyclophosphorothionate ([35S]TBPS) to the chloride channel/convulsant sites in membrane homogenates, nor for allosteric modulation of binding by GABA, the steroid anesthetic alphaxalone, or the benzodiazepine Ro 5-4864. In tissue section autoradiography, no difference was observed for these same assays nor for the binding of [3H]muscimol in the presence and absence of alphaxalone in several major regions. We conclude that circulating female sex hormones, possibly neurosteroid metabolites of progesterone, known to interact directly with the GABAA receptor complex, are involved in the sex differences in pentylenetetrazol seizure susceptibility.
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PMID:Sex differences in sensitivity to pentylenetetrazol but not in GABAA receptor binding. 133 80

The hemoglobin oxygenation state and the redox state of Cyt.ox. in the rat brain during and after seizure induced by PTZ were measured by using near-infrared spectrophotometry. PTZ administration caused transient reduction of Cyt.ox. in the brain, which might be a trigger for the increase of CBF during seizure. In postictal phase, although BP remained high, Cyt.ox. was in the certain reduced state, which might be due to A-V shunt. Hypoxic loading during seizure caused more reduction of Cyt.ox. than under non-epileptic conditions, which meant that seizure even under mild hypoxic conditions could cause severe hypoxic brain damage.
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PMID:Cerebral oxygenation state in chemically-induced seizures in the rat--study by near infrared spectrophotometry. 133 49

Combined forms of epileptic seizures are known to require combinations of antiepileptic drugs for their management. This study investigated the effects of such a combination consisting of phenobarbital and carbamazepine (mixed in the 1:4 ratio) as well as the effects of each component used separately on the Corazol-induced bioelectrical brain discharges. The effects were studied in a group of rats that received only a single dose of the drugs, as well as in a group that underwent 14-day anticonvulsant treatments. The bioelectric activity of the brain was recorded using an EEG method. In a single dosage, the combination of phenobarbital and carbamazepine was found to be more effective than its components. The decrease of Corazol-induced discharges was more pronounced in a single administration of the combination than when it was applied repeatedly. Development of a cumulative effect was observed in respect to carbamazepine action on the Corazol-induced discharges.
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PMID:Effects of phenobarbital, carbamazepine and a combination of both on corazol-induced changes in the bioelectric activity of rat brains. 133 68


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