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

Hindlimb extension (HLE) induced by maximal electroshock seizures (MES) can be markedly affected by drugs which affect CNS 5-hydroxytryptamine (5-HT). Consequently, it has been proposed that the natural resistance of certain rats (flexor rats) to HLE is due to elevated levels of 5-HT. We have tested the hypothesis that the increased resistance of flexor rats to MES-induced HLE is due to elevated serotonergic levels in some region(s) of the CNS by examining 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in 8 regions of the CNS in rats classified by MES as either flexors or extensors. Furthermore, we compared the in vivo synthesis rate of 5-HT between flexor and extensor rats in 6 regions of the brain by measuring the accumulation of 5-HTP following aromatic amino acid decarboxylase inhibition with NSD-1015. All neurochemical analyses were carried out on rats sacrificed one week after their last seizure test. No differences in 5-HT, 5-HIAA or 5-HTP synthesis rate were detected between flexor and extensor rats for any of the regions examined, suggesting that enhanced serotonergic levels are not responsible for the unusual resistance of flexor rats to HLE.
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PMID:Comparison of regional brain 5-HT and 5-HIAA content in flexor and extensor rats. 619 44

Inbred E1 mice are highly susceptible to convulsive seizures upon "throwing" stimulation. The strain is known to have an abnormal 5-hydroxytryptamine (5-HT) metabolism. In the study here 5-HT level, [14C]5-hydroxytryptophan (5-HTP) metabolism, MAO activity and [3H]5-HT receptor binding were examined in the cortex, brainstem and cerebellum. In the interictal period cortical and brainstem 5-HT level and [3H]5-HT receptor binding were significantly lower. In the same period cortical biosynthesized [14C]5-HT from [14C]5-HTP taken up was higher, and MAO activity was not changed. L-DOPA with MK486 induced a low threshold of seizures and decreased cortical 5-HT level. Abnormally functioning 5-HT neurones may exist in the E1 mouse cortex.
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PMID:Brain 5-hydroxytryptamine level, metabolism, and binding in E1 mice. 641 6

Pharmacological investigations of the ergot alkaloid of the group of clavines, elymoclavine, isolated from Claviceps sp. cp. II showed the following results: The LD50 for mice for 24 h was 350 (228-535) mg/kg and for rats 145 (81-258) mg/kg. Elymoclavine induced a dose-dependent stereotypy (doses of 2 to 10 mg/kg) in rats and mice which was antagonized by haloperidol and pimozide. It prevented the development of haloperidol catalepsy in rats and produced rotations contralateral to the striatal lesions with 6-OHDA which were antagonized by pimozide and partly by cyproheptadine. Elymoclavine, like bromocriptine, decreased the plasma level of prolactin. Furthermore, elymoclavine increased the exploratory activity of rats in open field; this effect was antagonized by haloperidol and was essentially influenced by many substances acting on different transmitter systems (NA, DA, GABA). Elymoclavine inhibited the picrotoxin and electroshock convulsive seizures but potentiated the pentylenetetrazol ones in mice as these effects were differently influenced by pimozide, haloperidol, 5-HTP, atropine and phentolamine. 100 and 250 micrograms/kg of elymoclavine produced a considerable and persisting decrease of the blood pressure in anaesthetized cats. At 1 X 10(-6) M, without producing any per se effect, elyoclavine decreased the contractile effects of acetylcholine, nicotine, BaCl2 and PGE1 as well as the field electrical stimulation-induced contractions in an isolated segment from guinea-pig ileum. The observed effects of elymoclavine are mainly due to its dopaminergic agonist action. It seems, however, that influences on other transmitter receptors also underlie the mechanism of action of this ergot alkaloid.
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PMID:On the pharmacology of the ergot alkaloid elymoclavine. 644 80

The effect of agents enhancing or diminishing serotonergic activity on seizures kindled from the rabbit amygdala was examined. Acute administration of 5-hydroxytryptophan (5-HTP) 10 and 25 mg/kg (administered in combination with a peripheral decarboxylase inhibitor), quipazine 1, 5 and 10 mg/kg or femoxetine 5 and 15 mg/kg which enhance serotonergic activity affected neither the intensity of behavioral seizures nor the duration of bioelectrical ones. 5-HTP 25 mg/kg and femoxetine 15 mg/kg prolonged the duration of behavioral seizures. Chronic administration of 5-HTP 25 mg/kg and femoxetine 15 mg/kg prolonged the duration of behavioral seizures. Chronic administration of 5-HTP 25 mg/kg had no effect on the development of kindled seizures. Acute administration of p-chlorphenylalanine (PCPA) 250 mg/kg reduced the intensity and shortened the duration of behavioral seizures. Cyproheptadine which blocks the postsynaptic action of serotonin shortened the duration of behavioral seizures. Chronic administration of PCPA 80 mg/kg delayed the development of kindled seizures. It is concluded that a pharmacological stimulation of the serotonergic system exerts no or little enhancing effect, whereas pharmacological inhibition of this system attenuates and delays the development of seizures kindled from the rabbit amygdala.
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PMID:Serotonergic mechanism in seizures kindled from the rabbit amygdala. 645 18

Experiments were performed to study the involvement of brain 5-HT in an experimental model of epilepsy induced by repeated electrical stimulation of the dorsal hippocampus of rats. The experiments included: (1) systemic injections of 5-hydroxytryptophan (5-HTP) and p-chlorophenylalanine (pCPA) and (2) electrolytic lesions of the midbrain raphe nuclei. The pCPA group showed a significant increase while animals which received systemic injections of 5-HTP showed a great reduction in the electrographic seizure activity. Although several reports have shown that midbrain raphe lesions do not modify the epileptic susceptibility, we observed a clear enhancement in the epileptiform activity in lesioned animals. The results presented here support the view that serotonergic systems may exert a tonic inhibitory effect on hippocampal epileptic activity.
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PMID:Effect of brain serotonin level on induced hippocampal paroxysmal activity in rats. 645 5

It was found previously that 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THbetaC) increased brain concentration of the neurotransmitter serotonin (5-HT) and decreased the concentration of its metabolite 5-hydroxyindole acetic acid (5-HIAA) at the same time the compound attenuated audiogenic seizures (AGS) in DBA/2J mice. In the present study we determined the time-course and dose-response effects of 6-MeO-THbetaC for blockade of AGS. Drugs sharing common effects with 6-MeO-THbetaC were also tested. At a dose of 100 mg/kg, 6-MeO-THbetaC blocked AGS between 10 min and 12 hr after injection, with maximal inhibition at 1 hr at which time a dose-related decrease in AGS was also demonstrated. All of the drugs tested which blocked AGS, including 6-MeO-THbetaC, THbetaC, 5-Hydroxytryptophan, chlorimipramine and pargyline, have biochemical similarities suggesting that facilitating serotonin function may be responsible for seizure-attenuating effects.
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PMID:Effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THbetaC) on audiogenic seizures in DBA/2J mice. 676 69

Pharmacological induction of changes in the serotonergic system was used to study the involvement of telencephalic serotonin (5-HT) in pinealectomy (PX) induced convulsions in the gerbil (Meriones unguiculatus). The reactions of the catecholamines norepinephrine (NE) and dopamine (DA) to both PX and drug treatment were also studied. Serotonin is apparently of little importance in the PX-induced convulsion since the artificial elevation by administration of tryptophan and 5-hydroxytryptophan, or depression by treatment with p-chloramphetamine, of telencephalic 5-HT had little effect on the convulsions. In other models for the study of epilepsy, lowered 5-HT results in an increase in seizure intensity. In this study, as in previous ones, telencephalic NE was repeatedly and significantly lowered after PX. None of the serotonergic drugs resulted in changes in NE. Data such as presented here are supportive of previous reports which indicate that a depression of NE facilitates convulsions.
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PMID:The involvement of brain amines in pinealectomy-induced convulsions in the gerbil: I. Serotonin. 697 73

The effect of alterations in whole brain monoamine content on the plasma lidocaine concentration resulting in seizures was studied in rats. Reductions in brain monoamine content were produced by treatment with one of the following drugs: reserpine, parachlorophenylalanine (PCPA), or alpha methyl paratyrosine (AMPT). Reserpine depleted norepinephrine (NE), and dopamine (DA) by 75 per cent and serotonin (5HT) by 54 per cent; PCPA reduced brain 5HT 56 per cent without changing NE and DA; AMPT reduced brain NE and DA by 54 and 60 per cent, respectively, without altering 5HT content. Treatment with 5-hydroxytryptophan, a serotonin precursor combined with the peripheral decarboxylase inhibitor RO4-4602 increased brain 5HT content by 400 per cent without changes in DA and NE. Whole brain NE concentrations were assayed fluorometrically, DA brain concentrations were assayed by HPLC, and lidocaine concentrations in plasma were determined by gas chromatography. Plasma lidocaine concentrations at the onset of convulsions were found to be elevated significantly only by drugs causing serotonin depletion; increasing to 128 per cent of control with reserpine treatment and 139 per cent of control with PCPA treatment. Depletion of NE and DA had no effect on the lidocaine seizure threshold. Increases in brain 5HT caused a small but not statistically significant decrease to 94 per cent of control in the mean plasma lidocaine concentration at seizure onset.
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PMID:Cerebral monoamines and lidocaine toxicity in rats. 705 26

4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a mixture of cis- and trans-4-(dimethylamino)spiro[cyclohexane-1,1'(3'H)-isobenzofuran]-3'-ones (1a,b), which were separated by fractional crystallization. Addition of aryllithium or aryl Grignard reagents to 1a,b and formic acid reduction afforded cis- and trans-4-(dimethylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofurans] 3a-f, which were converted to secondary amine analogues 5a-e. Tentative stereochemical assignments are based on chemical arguments and are supported by 13C NMR chemical shift data. Marked inhibition of tetrabenazine-induced ptosis is a property of most antidepressants, and significant antitetrabenazine activity is observed for several of these compounds. Optimal antitetrabenazine activity is associated with the cis-3'-phenyl series, and the cis secondary amine 5a is approximately twice as potent as the cis tertiary amine 3a. The various compounds are relatively weak with respect to potentiation of L-5-hydroxytryptophan-induced seizures.
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PMID:Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, 13C NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives. 724 20

The effects of intrahippocampally administered catechol- and indoleamines on the two types of hippocampal seizure discharges elicited by electrical and chemical stimulation were examined in unanesthetized rabbits. The catecholamines norepinephrine (NE) and dopamine (DA), injected into the hippocampus in doses of 100--200 micrograms, inhibited electrically induced hippocampal seizure discharges with a 50% increase in the stimulation threshold. However 5-hydroxytryptamine (5-HT) at doses of 50 micrograms to 100 micrograms caused no effect on electrically induced seizure discharges. On the contrary, 5-HT and 5-hydroxytryptophan (5-HTP) at a dose of 50 micrograms potentiated carbachol (5 micrograms)-induced hippocampal seizure discharges, prolonging the duration of seizure discharge three times the control. NE and DA had no effect on this chemically induced hippocampal discharges. It is therefore suggested that the effects of monoamines on hippocampal seizure discharges are very much dependent on the type of stimulation employed for the induction of this phenomenon.
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PMID:Effects of monoamines injected into the hippocampus on hippocampal seizure discharges in the rabbit. 727 94


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