Monoamines and the Pathophysiology of Seizure Disorders

Przegaliński, Edmund

doi:10.1007/978-3-642-69518-6_5

Cited by 18 publications

(7 citation statements)

References 100 publications

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“…Together with our previous findings (that TRH inhibited both seizures probably by releasing DA and absence-like seizures which were more pronounced in SER than in tremor rats), the decreased DA levels we observed may be the explanation for facilitation of the appearance of tonic convulsion and enhancement of absence-like seizures by causing decreased threshold of such seizures, although this is not the sole cause of the seizures. This conclusion is also supported by the findings that DA agonists inhibit convulsive seizures in kindled animals and other animal models of epilepsy (Jobe and Laird, 1981;Przegalinski, 1985;Loscher and Czuczwar, 1986).…”

Section: Discussionsupporting

confidence: 61%

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

et al. 1993

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Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tm/+) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure. DA and NE levels were also determined in age-matched male zitter, tremor and Kyo: Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10-12 weeks) SER, which showed epileptic seizures, and zitter rats than in adult Kyo: Wistar and tremor rats. DA levels in other areas such as thalamus-hypothalamus, midbrain, and pons medulla were not different among SER, zitter, tremor, and Kyo: Wistar rats at age 10-12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure-free SER (age 5 weeks) and young Kyo: Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo: Wistar rat, whereas in pons-medulla there was no difference between the two strains. In contrast, NE levels in the thalamus-hypothalamus, midbrain, cerebellum and pons-medulla were higher in SER and zitter rats at age 10-12 weeks than in age-matched tremor and Kyo: Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons-medulla of young SER as compared with young Kyo: Wistar rats. Turnover rates of NE were significantly lower in pons-medulla and cerebellum of the adult SER than in those of Kyo: Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 61%

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

et al. 1993

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“…With respect to tramadol and its enantiomers, in addition to mu receptor activation the inhibitory effects on monoamine uptake could be involved in the anticonvulsant activity observed at low doses of these compounds in the kindling model. It is well established that drugs enhancing serotonergic or noradrenergic activity exert anticonvulsant activity in different seizure models ( Kilian & Frey, 1973 ; Peterson & Albertson, 1982 ; Przegalinski, 1985 ; Corcoran & Weiss, 1990 ). Antidepressant drugs, which block the uptake of NE, 5‐HT, or both biogenic amines, were consistently shown to exert anticonvulsant activity after acute administration in fully kindled animals ( Stach et al ., 1980 ; Knobloch et al ., 1982 ; Clifford et al ., 1985 ; Minabe et al ., 1987 ; Yacobi & Burnham, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy

Potschka

Friderichs

Löscher

2000

British J Pharmacology

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1 The centrally acting analgesic tramadol has recently been reported to cause seizures at recommended dosages in patients, whereas animal experiments had indicated that seizures only occur in high, toxic doses. Tramadol has a dual mechanism of action that includes weak agonistic eects at the mu-opioid receptor as well as inhibition of monoamine (serotonin, norepinephrine) re-uptake. Its major (M1) metabolite mono-O-desmethyltramadol, which is rapidly formed in vivo, has a markedly higher anity for mu receptors and may thus contribute to the eects of the parent compound. Furthermore, the pharmacological eects of tramadol appear to be related to the dierent, but complementary and interactive pharmacologies of its enantiomers. In the present study, we evaluated (+)-tramadol, its enantiomers, and its M1 metabolite ((+)-enantiomer) in the amygdala kindling model of epilepsy in rats. Adverse eects determined in kindled rats were compared to those in nonkindled rats. 2 At doses within the analgesic range, (+)-tramadol and its enantiomers induced anticonvulsant eects in kindled rats. However, at only slightly higher doses seizures occurred. With (+)-tramadol, generalized seizures were observed at 30 mg kg 71 in most kindled but not in nonkindled rats. The (7)-enantiomer induced myoclonic seizures at 30 mg kg 71 in most kindled but not in nonkindled rats, although myoclonic seizure activity was observed in some nonkindled rats at 10 or 20 mg kg 71 . Seizures were also observed after the (+)-enantiomer and the (+)-enantiomer of the M1 metabolite, but experiments with higher doses of these compounds were limited by marked respiratory depression. 3 The data demonstrate that kindling enhances the susceptibility of rats to convulsant adverse eects of tramadol and its enantiomers, indicating that a preexisting lowered seizure threshold increases the risk of tramadol-induced seizures.

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Section: Brain 5‐ht Concentration and Epilepsymentioning

confidence: 99%

“…Serotonergic neurotransmission modulates a wide variety of experimentally induced seizures and is involved in the enhanced seizure susceptibility observed in rodents genetically prone to epilepsy (Kilian and Frey 1973;Buterbaugh 1978;Przegalinski 1985;Hiramatsu et al 1987;Dailey et al 1992;Gerber et al 1998;Filakovszky et al 1999). Generally, agents that elevate extracellular 5-HT levels, such as 5hydroxytryptophan and 5-HT reuptake blockers, inhibit both focal (limbic) and generalized seizures (Löscher 1984;Prendiville and Gale 1993;Yan et al 1994).…”

Section: -Ht Release In Spontaneous and Evoked Seizuresmentioning

confidence: 99%

Serotonin and epilepsy

Bagdy

Kecskeméti

Riba

et al. 2006

Journal of Neurochemistry

305

216

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In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT 1A , 5-HT 2C , 5-HT 3 and 5-HT 7 receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT 1A or 5-HT 2C receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT 1A receptors and depolarization of GABAergic neurons by 5-HT 2C receptors as well as antagonists of 5-HT 3 and 5-HT 7 receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies.

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Monoamines and the Pathophysiology of Seizure Disorders

Cited by 18 publications

References 100 publications

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy

Serotonin and epilepsy

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