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

In order to further elucidate the possible role of histamine in the seizure model, we determined the histamine levels in different brain regions of genetically epilepsy-prone Krushinski-Molodkina (KM) rats. Histamine levels in the striatum, hippocampus, amygdala, midbrain, thalamus and hypothalamus of KM rats were significantly lower than in the epilepsy-resistant Wistar rats. Previously, we have reported that the audiogenic seizures of KM rats were reduced by metoprine, which can markedly increase brain histamine. These findings are in agreement with the hypothesis that central histamine neuron system may be involved in the inhibitory mechanism of seizures.
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PMID:Strain differences in regional brain histamine levels between genetically epilepsy-prone and resistant rats. 161 66

The first indication that histamine might be important in the functioning of the brain was the finding that the centrally penetrating histamine H1 antagonists had marked sedative properties. Subsequently with the development of more specific compounds and drugs for the H1, H2 and H3 receptors a greater understanding of the neurotransmitter/modulator role of histamine in the CNS has been possible. Histamine is now associated with wakefulness, suppression of seizures, hypothermia and emesis. The histamine H1 antagonists have been shown to potentiate opioid-induced analgesia, and modify eating and drinking patterns as well as endocrine secretions from the pituitary gland. Additionally, clinically useful antidepressants have been shown to inhibit histamine-sensitive adenylate cyclase from the mammalian brain. Recently, a possible role for both histamine H1 and H2 receptors in schizophrenia has been reported. As more specific and centrally-penetrating histaminergic compounds are developed, so the roles of histamine as a neurotransmitter/modulator in the brain will be better understood.
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PMID:Histaminergic drugs as modulators of CNS function. 873 45

First-generation H1-antagonist-induced central toxicity often includes psychiatric changes, seizures and hallucinations, commonly thought to result from their central anticholinergic effects. Interference with the central functions of histamine have not been adequately addressed, despite the identification of histamine as a central neurotransmitter and neuromodulator. A synthesis of data support antagonism of H1-receptors as critical to the CNS toxicity of these drugs. The histaminergic neuronal system (HNS) is involved in a variety of global brain functions. Inherent or induced alterations in the HNS are associated with behavioral disorders. Clinical and experimental evidence support a role for the HNS in seizure protection and a relationship exits between histamine regulated systems and seizures. Histamine has important neuromodulatory influences on the central electrophysiology which underlies normal thalamocortical function. H1-antagonists block the H1-receptor-mediated reduction of a background-leakage K+ current (IKL) in central neurons. Secondary alterations in other ionic currents and alterations in synaptic responses to glutamate and GABA are produced. The non-H1 receptor-mediated effects of histamine persist in the presence of these drugs, contributing to imbalances in central electrophysiology. H1-antagonist-induced changes are similar to the electrical disturbances thought to underly epileptic seizures and may adequately explain their hallucinogenic activity. These data form the basis for this review and must be considered as a major mechanism for the CNS toxicity of the first-generation H1-antagonists.
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PMID:Role of the central histaminergic neuronal system in the CNS toxicity of the first generation H1-antagonists. 918 37

Histamine is implicated in the regulation of brain functions through three distinct receptors. Endogenous histamine in the brain is derived from mast cells and neurons, but the importance of these two pools during early postnatal development is still unknown. The expression of histamine H1-receptor in the rat brain was examined using in situ hybridization during postnatal development and in adults. For comparison, the expression of L-histidine decarboxylase (HDC) in the two pools was revealed. H1-receptor was evenly expressed throughout the brain on the first postnatal days, but resembled the adult, uneven pattern already on postnatal day 5 (P5). HDC was expressed in both mast cells and tuberomammillary neurons from birth until P5, after which the mast cell expression was no more detectable. In adult rat brain, high or moderate levels of H1-receptor expression were found in the hippocampus, zona incerta, medial amygdaloid nucleus and reticular thalamic nucleus. In most areas of the adult brain the expression of H1-receptor mRNA correlates well with binding data and histaminergic innervation. A notable exception is the hypothalamus, with high fibre density but moderate or low H1-receptor expression. Systemic kainic acid administration induced increased expression of H1-receptor mRNA in the caudate-putamen and dentate gyrus, whereas no change was seen in the hippocampal subfields CA1-CA3 or in the entorhinal cortex 6 h after kainic acid injections. This significant increase supports the concept that histaminergic transmission, through H1-receptor, is involved in the regulation of seizure activity in the brain.
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PMID:Postnatal expression of H1-receptor mRNA in the rat brain: correlation to L-histidine decarboxylase expression and local upregulation in limbic seizures. 974 57

Susceptibility to behaviorally similar audiogenic seizures (AGS) occurs genetically and is inducible during ethanol withdrawal (ETX). Comparisons between AGS mechanisms of genetically epilepsy-prone rats (GEPR-9s) and ethanol-withdrawn rats (ETX-Rs) are yielding information about general pathophysiological mechanisms of epileptogenesis. The inferior colliculus (IC) is the AGS initiation site. Excitatory amino acid (EAA) abnormalities in the IC are implicated in AGS, and histamine and adenosine receptor activation each reduce EAA release and inhibit several seizure types. Previous studies indicate that focal infusion of an adenosine receptor agonist into the IC blocked AGS in GEPR-9s, but the effects of adenosine receptor activation in the IC on AGS in ETX-Rs are unknown. The effects of histamine receptor activation on either form of AGS are also unexamined. The present study evaluated effects of histamine or a nonselective adenosine A(1) agonist, 2-chloroadenosine, on AGS by focal microinjection into the IC. Ethanol dependence and AGS susceptibility were induced in normal rats by intragastric ethanol. Histamine (40 or 60 nmol/side) significantly reduced AGS in GEPR-9s, but histamine in doses up to 120 nmol/side did not affect AGS in ETX-Rs. 2-Chloroadenosine (5 or 10 nmol/side) did not affect AGS in ETX-Rs, despite the effectiveness of lower doses of this agent in GEPR-9s reported previously. Thus, histamine and adenosine receptors in the IC modulate AGS of GEPR-9s, but do not modulate ETX-induced AGS. The reasons for this difference may involve the chronicity of AGS susceptibility in GEPR-9s, which may lead to more extensive neuromodulation as compensatory mechanisms to limit the seizures compared to the acute AGS of ETX-Rs.
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PMID:Modulation of audiogenic seizures by histamine and adenosine receptors in the inferior colliculus. 1078 66

The role of central histamine in amygdaloid kindled seizures in rats was studied. Histamine content in the amygdala was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H1-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine- or histidine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and i.p. injections of H3-antagonists (thioperamide, AQ0145 and clobenpropit) resulted in a dose-related inhibition of amygdaloid kindled seizures. The effects of thioperamide and AQ0145 were inhibited by an H3-agonist (R)-alpha-methylhistamine and H1-antagonists. On the other hand, H2-antagonists showed no antagonistic effect. GABAmimetic drugs, diazepam, sodium valproate and muscimol potentiated the effect of clobenpropit. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H1-receptors. In addition, an inhibition of amygdaloid kindled seizures induced by histamine is closely related with the action of GABA.
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PMID:[Role of central histamine in amygdaloid kindled seizures]. 1141 42

Effects of histaminergic agonists and antagonists were investigated on withdrawal signs in lorazepam-dependent rats. Physical dependence was developed by giving lorazepam admixed with the food in the following dose schedule (in mg/kg given daily x days): 10 x 4, 20 x 4, 40 x 4, 80 x 4, and 120 x 7. The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot shock aggression (FSA), and audiogenic seizures. During the withdrawal period, the rats were divided into groups of 10 each. Control-withdrawal group did not receive any drug. The drugs (in mg/kg administered intramuscularly)--L-histidine (50), histamine-N-methyl (2), promethazine (10), pheniramine (10), astemizole (10), and thioperamide (1)--were given separately in other groups daily during the withdrawal period. The withdrawal signs in control group were hyperkinesia, hyperaggression, and audiogenic seizures. L-Histidine, precursor of histamine, and thioperamide, antagonist of H3 receptor, potentiated hyperkinesia, hyperaggression, and audiogenic seizures. Histamine-N-methyl, agonist of H3 receptor, and H1 receptor antagonists, promethazine and pheniramine, blocked all the withdrawal signs. Astemizole, a peripheral antagonist of H1 receptor, could not affect any withdrawal sign. It may be concluded that histamine H1 receptors are facilitatory and H3 receptors are inhibitory for benzodiazepine (BZD) withdrawal syndrome.
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PMID:Role of central histaminergic system in lorazepam withdrawal syndrome in rats. 1152 76

Histaminergic activity shows a clear circadian rhythm: high levels during the active period (in rodents at night, in monkeys and humans during the day), and low levels during the sleep period. Histamine appears to be necessary for the maintenance of the circadian rhythmicity of the adrenocortical hormone release, locomotor activity and food intake, and the sleep-wakefulness cycle. In addition, a role for histaminergic neurons in the light entrainment is implicated. In phase shift studies, histamine given centrally seems to entrain the activity rhythm in the same way as light impulses and inhibition of histamine synthesis seems to block the entrainment by light. Importantly, histamine participates in the control of arousal and may be implicated in the sleep disturbances in hepatic encephalopathy. Furthermore, evidence suggests a role for histamine in overall neuronal excitability and seizure susceptibility both in animals and humans. Thus, we conclude that histamine may exert modifying effects on circadian rhythmicity and neuronal excitability.
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PMID:Modifying effects of histamine on circadian rhythms and neuronal excitability. 1164 Sep 65

The involvement of central histamine in amygdaloid kindled seizures in rats was investigated using histamine-related compounds. Histamine contents in the amygdala of electrical stimulation site was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H(1)-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H(1)-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine (i.c.v.)-induced inhibition of amygdaloid kindled seizures, however, no significant antagonism was observed with H(2)-antagonists (cimetidine, ranitidine or zolantidine). Intracerebroventricular injection of H(3)-antagonists (thioperamide and AQ 0145) resulted in a dose-related inhibition of amygdaloid kindled seizures. The same findings were observed when thioperamide and clobenpropit were injected i.p. The effects of thioperamide (i.p.) and AQ 0145 (i.p.) were inhibited by an H(3)-agonist [(R)-alpha-methylhistamine] and H(1)-antagonists (diphenhydramine and chlorpheniramine). On the other hand, H(2)-antagonists (cimetidine and ranitidine) showed no antagonistic effects. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H(1)-receptors.
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PMID:Involvement of central histamine in amygdaloid kindled seizures in rats. 1164 Sep 77

Experimental and epidemiological studies have indicated that central histaminergic neuron system plays an important role in inhibition of convulsive disorders through histamine H(1)-receptors, especially in developing period. Histamine H(1) antagonists increase the duration of electrically induced convulsions in 21-day-old mice, but not in 42-day-old mice. Epidemiological studies suggested that histamine H(1) antagonist may be one of the risk factors in febrile convulsions. In histidinemic patients who were considered to have high brain histamine content, the incidence of convulsions was lower than that of ordinary population.The centrally acting histamine H(1) antagonists including pyrilamine and ketotifen facilitate the development of amygdaloid kindling in rats, an experimental model of epileptogenic process. On the contrary, epinastine, a histamine H(1) antagonist which scarcely enters the brain, shows no facilitation. These findings suggest that the central histaminergic neuron system plays an inhibitory role on the seizure development through central histamine H(1)-receptors.Recently, three cases has been reported in which West syndrome developed 8-10 days after ketotifen or oxatomide administration. Considering experimental and clinical studies, histamine H(1) antagonists may be associated with West syndrome and may be hazardous to infants. Further careful experimental and clinical studies will be required to elucidate the relationships between West syndrome and central histaminergic neuron system.
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PMID:The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain. 1170 Dec 52


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