The role of norepinephrine in epilepsy: from the bench to the bedside

Giorgi, Filippo Sean; Pizzanelli, Chiara; Biagioni, Francesca; Murri, Luigi; Fornai, Francesco

doi:10.1016/j.neubiorev.2004.06.008

Cited by 157 publications

(121 citation statements)

References 161 publications

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“…However, in mice, 5HT loss is milder, while a severe DA depletion occurs, as described in detail by the Colado's group (Colado et al, 2001) and shown by other studies (Stone et al, 1987;Logan et al, 1988;Ali et al, 1991;Cadet et al, 1995;Fornai et al, 2001Fornai et al, , 2004b. Both monoamines might modulate seizures (see, for instance, Pasini et al, 1996;Starr, 1996;Heisler et al, 1998;Torta and Monaco, 2002;Giorgi et al, 2003Giorgi et al, , 2004. However, this is unlikely to occur in the present study.…”

Section: Discussionsupporting

confidence: 63%

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

et al. 2005

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Section: Discussionsupporting

confidence: 63%

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

et al. 2005

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“…The observed effects on brain NA concentrations suggest that HEPB acts on NA receptors or transporters and that these actions could involve other catecholamines. The proposed mechanism of action of HEPB is consistent with the data obtained from multiple experimental models that converge to demonstrate the antiepileptic role of endogenous NA (15). This effect mostly counteracts the development of an epileptic circuit rather than increasing the epileptic threshold.…”

Section: Resultssupporting

confidence: 82%

“…Interestingly, studies have also indicated a role for dopamine (DA) (13,14) and noradrenaline (NA) (15) in regulating seizure activity in the brain. Moreover, the depressive effect of GBL, a precursor drug of EFBL, is attributed to the selective increase in DA concentration that it causes in mouse, rat and rabbit brains (1).…”

mentioning

confidence: 99%

Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

2017

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Effect of g-ethyl-g-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels g-Ethyl-g-phenyl-butyrolactone (EFBL) is a structural combination of the anticonvulsant g-hydroxy-g-ethyl-g-phenylbutyramide (HEPB) and the hypnotic g-butyrolactone (GBL), which inherits both properties. To clarify its mechanism of action, the effects of EFBL, GBL and HEPB on dopamine (DA) and noradrenaline (NA) brain levels were investigated. Influences of chlorpromazine, phenelzine and aminooxyacetic acid were also studied. EFBL increased DA in a dose-dependent manner, remaining enhanced by 80 % over a period of 24 h and augmented NA by 54 % one hour after treatment. HEPB increased DA and NA approximately 2-fold after the first hour. GBL raised DA and NA after three and 24 h, resp. EFBL reversed chlorpromazine effects but potentiated those of phenelzine on DA. Amino-oxyacetic modified neither DA nor NA brain levels, not even in the presence of EFBL. The anticonvulsant and hypnotic properties of EFBL are attributed to its effect on presynaptic dopaminergic receptors and its lasting effect on ethyl and phenyl radicals that hinder its degradation. The results support the role of DA and NA in regulating seizure activity in the brain and indicate that EFBL offers a potential treatment for refractory epilepsy without complementary drugs and Parkinson's disease, without the drawbacks of oral therapies. : g-ethyl-g-phenyl-butyrolactone (EFBL), anticonvulsant, hypnotic, mouse brain, catecholamine It is known that g-butyrolactone (GBL) has depressant effects on the central nervous system (CNS), causing sleepiness and anesthesia (1), whereas ethyl-phenyl-pyrrolidinone (EPP), the cyclic form of g-aminobutyric acid (GABA), is an anticonvulsant whose structure is known as g-hydroxy-g-ethyl-g-phenylbutyramide (HEPB). As a result of the structural combination of HEPB and GBL, g-ethyl-g-phenyl-butyrolactone (EFBL) was synthesized (2), showing both anticonvulsant (2, 3) and hypnotic (4) properties. Because of the abovementioned pharmacological properties, the mechanism of action of EFBL was investigated. It is fundamental to understand the role of GABA, a major inhibitory neurotransmitter in the CNS of mammals, in neuronal excitability, to fully comprehend its mechanism of action and rational design of anticonvulsant agents (5). Since an association between the activity of the GABA-synthesizing enzyme L-glutamate decarboxylase (DAG) and seizure generation was established, increasing the brain GABA levels has become a common strategy utilized in the rational design of anticonvulsants. One approach to accomplishing this goal has been the inhibition of the GABA-degrading enzyme GABA-transaminase (T-GABA). T-GABA inhibitors, such as hydroxylamine and amino-oxyacetic acid (AAOA), have been shown to protect against seizures induced by different chemoconvulsants (6). In any case, most anticonvulsants used in epilepsy treatment are related to GABA-ergic transmission. Therefore, we aimed to clarify the mechanism o...

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“…It is likely that METH-induced glutamate release in limbic brain regions may reach the threshold to trigger convulsive seizures in the absence of endogenous NE. In fact, METH is a powerful glutamate releaser [67-69], while NE is considered to be a pivotal endogenous seizure suppressive mechanism [20, 140-143]. …”

Section: The Role Of Ne In Methamphetamine-induced Behavioural Changesmentioning

confidence: 99%

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

Ferrucci

Giorgi

Bartalucci

et al. 2013

Current Neuropharmacology

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The activity of locus coeruleus (LC) neurons has been extensively investigated in a variety of behavioural states. In fact this norepinephrine (NE)-containing nucleus modulates many physiological and pathological conditions including the sleep-waking cycle, movement disorders, mood alterations, convulsive seizures, and the effects of drugs such as psychostimulants and opioids. This review focuses on the modulation exerted by central NE pathways on the behavioural and neurotoxic effects produced by the psychostimulant methamphetamine, essentially the modulation of the activity of mesencephalic dopamine (DA) neurons. In fact, although NE in itself mediates some behavioural effects induced by methamphetamine, NE modulation of DA release is pivotal for methamphetamine-induced behavioural states and neurotoxicity. These interactions are discussed on the basis of the state of the art of the functional neuroanatomy of central NE- and DA systems. Emphasis is given to those brain sites possessing a remarkable overlapping of both neurotransmitters.

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The role of norepinephrine in epilepsy: from the bench to the bedside

Cited by 157 publications

References 161 publications

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

Previous exposure to (±) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility

Effect of γ-ethyl-γ-phenyl-butyrolactone (EFBL), anticonvulsant and hypnotic drug, on mouse brain catecholamine levels

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

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