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

Several new lines of evidence suggest the existence of two or more distinct types of benzodiazepine receptors, in contrast to earlier results suggesting the presence of only one class of receptors. Appropriate thermoinactivation experiments indicate two receptors with different thermostabilities. Several triazolopyridazines, with some of the pharmacological properties of anxiolytics have recently been shown to displace 3H-diazepam and 3H-flunitrazepam with Ki values in the 6 to 100 nanomolar range. These new substances are active in conflict tests in rats and monkeys and prevent metrazol induced seizures in vivo, but strikingly lack the ataxia and sedative properties of the benzodiazepines. Hill analyses of dose-response curves for some of these substances yields Hill coefficients in the range of 0.4--0.6, suggesting that these compounds may be able to discriminate between several types of benzodiazepine receptors.
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PMID:Some properties of brain specific benzodiazepine receptors: new evidence for multiple receptors. 4 Feb 57

The antagonism of various seizure and time-related components of the convulsions resulting after IV injection of D,L-allylglycine into male Wistar rats were assessed in a standard test procedure. Trimethadione and ethosuximide did not antagonize the seizure components, whereas clonazepam, phenobarbital, diphenylhydantoin, primidone, valproate sodium, aminoxyacetic acid, etomidate, acetazolamide, flunarizine, pipamperone and baclofen did. The allylglycine test may thus represent a relatively specific method of differentiating between drugs effective against partial or generalized convulsive seizures from those effective against absence seizures. The neuroleptics haloperidol and pimozide were completely inactive in contrast to their reported antagonism of bicuculine seizures. The spectra of the active substances are discussed with respect to Principal Component and Cluster Analysis. Noteworthy are the similarities between baclofen and etomidate; between aminoxyacetic acid, phenobarbital and valproate sodium; and between diphenylhydantoin and flunarizine.
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PMID:Effects of some anti-epileptic, neuroleptic and gabaminergic drugs on convulsions induced by D,L-allylglycine. 4 Dec 64

The existence of specific receptor sites for benzodiazepines has been well documented by in vitro binding studies. In this study, using a highly radiolabelled [3H]-flunitrazepam, we investigated the binding of benzodiazepines to their receptor sites under in vivo conditions. Tracer doses of [3H]flunitrazepam (0.001 mg/kg) were injected i.v. into mice and the concentration of the drug in the brain was monitored. The accumulation of [3H]flunitrazepam 20 min after injection was found to be highest in the hippocampus, cortex, hypothalamus; to be intermediate in the striatum, medulla oblongata/pons and midbrain and to be lowest in the cerebellum. This corresponds well with the different densities of benzodiazepine receptors which we found in in vitro studies, with the exception of medulla oblongata/pons and cerebellum. When increasing doses (0.01--10 mg/kg) of non-labelled benzodiazepine derivatives (flunitrazepam, clonazepam, the 3S and 3R enantiomers of 5-(o-fluorophenyl)-1,3-dihyrdo-1,3-dimethyl-7-nitro-2H-1,4-benzodiazepine-2-one, and chlordiazepoxide) were injected simultaneously with [3H]flunitrazepam, a dose-dependant, saturable and and stereo-specific decrease of [3H]flunitrazepam concentration in the mouse hippocampus was observed. The dose range in which the unlabelled benzodiazepines decreases the levels of [3H]flunitrazepam in the hippocampus corresponds closely to that which inhibited pentylenetetrazol- or picrotoxin-induced seizures, indicating that this in vivo method determines the occupation of pharmacologically relevant receptors.
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PMID:In vivo receptor occupation by benzodiazepines and correlation with the pharmacological effect. 4 15

The steady rise in the promiscuous use of phencyclidine (PCP) as a "recreational" drug has recently gained nationwide attention because of the numerous violent and/or bizarre incidents caused by the use of this drug. Because the media often exaggerate reports of bizarre and violent behavior to make a "good" story, the potential PCP user may be tempted to ignore the media warnings. In the case of PCP, however exaggerated the story, a real danger does exist. So, despite numerous newspaper, radio and television warnings about the possible consequences of PCP use and abuse, the incidence of toxic reactions continues to climb. In many cases PCP is sold as other drugs, particularly THC, and in various colored capsules, tablets, liquids and crystals which may explain the increased usage despite the numerous warnings against its use. The advances in laboratory techniques and chemical processess have enabled the clandestine chemist to prepare relatively pure PCP and thus eliminate many of the toxic side effects due to impurities in the drug. In addition, 30 or more psychoactive PCP analogues have been developed and are starting to make an appearance on the street. PCP is perhaps the most potent psychotomimetic compound known at the present time and is capable of inducing a psychosis which is clinically indistinguishable from schizophrenia. The psychosis-producing effects of PCP are the most common toxic effects seen in hospital emergency rooms; but as the amount of PCP taken and/or the simultaneous involvement of other drugs, particularly barbiturates, occurs, severe medical problems (e.g., coma, seizures, respiratory arrest) begin to appear. Death from high doses of PCP or PCP plus other drugs does occur, but the principal cause of death from PCP abuse is due to trauma, homicide or suicide (usually of the bizarre or violent form). Young adult males, persons predisposed to mental illness and naive drug users appear to be the most susceptible to the adverse effects of PCP. The fact that chronic PCP users are starting to increase in number is mute testimony that not all users experience "bad trips" with PCP. Unfortunately for the user, however, this does not guarantee that the next trip will not be a bad one. The effects of chronic use seem to be twofold: severe depression with suicidal thoughts and numerous violent, agitated behavioral patterns. Neither seems to be a suitable alternative. At the present time there is not specific antidote for toxic PCP reactions and the prolonged psychosis induced in some cases does not appear to respond to the standard antipsychotic medications as quickly as do the functional psychoses. The major improvement from a medical standpoint is the development of more sensitive laboratory techniques to confirm the presence of PCP in body fluids. This advance has undoubtedly led to the apparent increase in the number of PCP cases reported by hospitals and to the accuracy of clinical diagnosis by medical, drug or law enforcement communities...
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PMID:PCP (phencyclidine): an update. 4 8

The aim of the present study was to correlate locally at the same pial artery the vascular reaction with the perivascular pH during the initial phase of functional hyperemia. As a model of functional hyperemia, bicuculline (3 mg/kg i.v.) induced seizure was taken. Normally, a strong increase of blood pressure occurs together with the start of seizure. Since a discrimination between metabolically induced and pressure dependent vascular reactions is not possible under such conditions, the cats (anesthetized with 40--50 mg/kg chloralose) received in addition 3 mg/kg phentolamine and 10 mg/kg pentobarbital. Under these conditions a significant increase of blood pressure started only 50 s after the onset of seizure. Perivascular pH was recorded using spear type pH microelectrodes in the subarachnoid space surrounding a pial artery. The diameter of the respective artery was measured continuously. After onset of seizure an immediate, increasing perivascular acidosis developed which was accompanied by an increase in pial arterial diameter. The maximal decrease of pH was 0.29 units and occurred 30 s after the start of seizure. These data show that a decrease in perivascular pH can be one factor mediating functional hyperemia in the brain.
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PMID:Perivascular pH and pial arterial diameter during bicuculline induced seizures in cats. 4 74

Acute hypertension increases the cerebrovascular permeability to protein to a higher extent in anesthetized than in conscious rats. When hypertension is combined with a pronounced cerebral vasodilatation, e.g. in bicuculline-induced seizures, the protein leakage is enhanced. Conscoius, unrestrained 2--3-months-old rats received adrenaline or bicuculline i.v. during continuous recording of the mean arterial pressure and were killed 3 minutes later. Rats, neonatally sympathectomized by 6-hydroxydopamine, had significantly increased extravasation of 125I serum albumin in the brain after adrenaline-induced hypertension than nonsympathectomized rats. Since transection of the cervical sympathettic trunk alone does not have the same effect, a protection of the blood-brain barrier in acute hypertension in conscious rats may, at least in part, be mediated via the central noradrenergic innervation of cerebral vessels. Bicuculline did not increase blood pressure in 6-OHDA treated rats; thus the blood-brain barrier remained intact.
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PMID:Neonatal 6-hydroxydopamine treatment increases the vulnerability of the blood-brain barrier to acute hypertension in conscious rats. 4 65

Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.
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PMID:Lorazepam in status epilepticus. 4 12

Our group has been carrying out interdisciplinary studies on the effects of prenatal and postnatal protein malnutrition on the developing rat brain. Anatomical, physiological, biochemical and behavioral approaches using the same animal model have revealed that protein malnutrition affects the brain at various levels, i.e., (1) anatomical, as revealed by Golgi findings of deranged dendritic trees on analysis of cortical and subcortical areas; (2) physiological, as revealed by delayed sleep pattern maturation, disturbances in seizure thresholds, slowing of sensory cortico-cortical and thalamocortical evoked potentials, and changed power in hippocampal theta activity; (3) biochemical, as revealed by marked increases in biogenic amines dating from birth, as well as modifications in tryptophan metabolism; and (4) behavioral, as revealed by various changes in responses to different kinds of aversive stimulation. Reversal studies have revealed that many changes are permanent and not amenable to nutritional rehabilitation even at birth, which is before the brain growth spurt in the rat. Our paradigm closely mimicks the human condition of low level, chronic protein undernutrition and thus reveals the underlying disturbances due to malnutrition. The dietary reversal studies are attempts at pin-pointing critical brain growth periods, beyond which recovery of functions is not possible.
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PMID:Developmental protein malnutrition: influences on the central nervous system of the rat. 4 55

The ability of midbrain homogenates from two strains of mice to accumulate several putative neurotransmitters, or their precursor in the case of acetylcholine, has been examined. The high-affinity transport mechanisms toward glutamate, GABA, dopamine, and glycine were similar in both strains. The seizure-prone DBA21BG strain had a significantly higher capacity to transport choline than did the relatively seizure-resistant C57BL/6 IBC mice. Howaver, no difference in the density of muscarinic binding sites in the two mouse strains was found.
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PMID:Seizure proneness and neurotransmitter uptake. 4 44

The unilateral and bilateral therapy differ in psycho-organic effects but have the same antidepressive efficiency. This is due to the facts that the organic effects are mainly caused by the electrical current whereas the antidepressive effect is dependent on the seizure activity. Compared to the bilateral treatment, unilateral gives reduced confusion, anterograde and retrograde amnesia as well as reduced experience of memory impairment. The difference is explained by a lower density of current in the brain. The unilateral treatment should be the treatment to be chosen. The antidepressive action of ECT fits the amine hypothesis, ECT causes a sustained increase of the synthesis of norepinephrine and of the sensitivity of amine receptors and creates conditions for alleviating both "low-output" and "low-sensitivity" depression. The antidepressive action is probably mediated by release of hypothalamic neurohormones.
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PMID:[Unilateral and bilateral shock therapy: mechanism of action (author's transl)]. 4 67


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