Duration Of Convulsions Research Articles

Study of plant anticonvulsants

In Nigeria, convulsion, especially in children, is managed by traditional healers employing plant decoctions. A number of herbs are used for this purpose. We have carried out some preliminary studies on some of these traditional anticonvulsant plants. The experimental models were pentylenetetrazole- and electroshock-induced convulsions in mice. The acute toxicity (LD50) and the median effective (ED50) doses of the extracts of these plants were determined. Most of these plants exhibited potent anticonvulsant activity. The average onset of convulsion was delayed, while the average duration of convulsion was significantly reduced. Most of the animals showed signs of central nervous system depression. The results indicate that these plants possess anticonvulsant property, and this activity may be linked to their ability to depress the central nervous system.

Effect of an ascending dose regimen on the development of tolerance to the anticonvulsant effect of diazepam.

The effect of an ascending dose regimen on the development of tolerance to diazepam's anticonvulsant effect was assessed. During the 22 trials of the tolerance development phase, amygdala-kindled rats received either a series of dosage injections ranging from high (10 mg/kg), to low (1.0 mg/kg), and ascending (1.0 mg/kg and increased by 0.2-mg/kg increments to 3.0 mg/kg) or saline injections. Diazepam was administered by ip injection once every 48 hr, and each injection was followed 1 hr later by a convulsive stimulation. The ascending dose rats displayed significantly more tolerance to the anticonvulsant effect of diazepam than did the high dose, low dose, or saline rats. By contrast, both the ascending and high dose rats displayed a significant withdrawal effect (i.e., increased duration of convulsions) after the cessation of diazepam injections. Results demonstrate that administration of ascending dosages can facilitate the development of tolerance to anticonvulsant drug effects and that tolerance and withdrawal are not necessarily inextricably related.

A reappraisal of the role of caffeine in ECT.

Caffeine lengthens ECT seizures, perhaps by lowering the convulsive threshold. The authors assessed the impact of caffeine on the convulsive threshold and seizure duration. The convulsive threshold and seizure durations of 12 inpatients receiving right unilateral ECT were determined with and without caffeine pretreatment. Caffeine did not change the convulsive threshold, but it did lengthen seizure duration. Caffeine's lengthening of seizure duration without affecting the convulsive threshold is an uncertain benefit in right unilateral ECT.

Effect of an adenosine A 1 agonist injected into substantia nigra on kindling of epileptic seizures and convulsion duration

The substantia nigra pars reticulata (SNr) has been reported to be critically involved in the development and propagation of epileptic seizures, while extracellular adenosine appears to be important for making seizures stop. In the present study, an adenosine A 1 receptor agonist [N 6-cyclohexyladenosine (CHA); 2.0 nmol/side, or vehicle] was injected bilaterally into the SNr shortly before each of the first five of a series of daily kindling stimuli delivered to the rat amygdala. Injections did not affect the acquisition of kindled afterdischarges or the rate at which seizures developed over subsequent kindling sessions, but convulsions occurring 48–72 h after treatment were significantly shortened. Thus, purinergic mechanisms in the SNr do not appear to be specifically involved in the acquisition of kindled seizures but may contribute to a postictal inhibitory process that shortens the convulsive component.

Risk factors for recurrence of febrile convulsions.

A cohort of hundred children with febrile convulsions, in the age group of 3 months to 5 years were followed up prospectively for one year to study the natural course of the illness, and to determine if specific factors would increase the risk of recurrence of febrile convulsions. The risk factors studied were age of onset under one year, long duration of convulsion (more than 15 minutes), family history of febrile convulsion or epilepsy and combination of two or all of the above factors. Four groups of children with different risk factors were followed up for recurrence of convulsion, after the first attack. A group of children without any risk factor was considered as control and they were also followed up for recurrence of convulsions. Though all the groups with the risk factors, showed a trend towards a higher recurrence rate when compared to controls, the difference observed clinically was not significant statistically. This could be due to the small sample size of each group. A larger study could throw light on the predictive value of these risk factors and narrow down the use of long term anticonvulsant prophylaxis.

Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of alpha-fluoromethylhistidine and metoprine.

The purpose of this study was to investigate the possible role of the central histaminergic neuron system in electrically-induced seizure in mice. For this purpose, we examined the effects of intraperitoneal (i.p.) injections of histaminergic agents, such as L-histidine, metoprine, and alpha-fluoromethylhistidine (FMH), on electrically-induced seizure. L-Histidine decreased the duration of clonic convulsion in electrically-induced seizure, but not affected that of tonic convulsion. This effect of L-histidine was antagonized by pretreatment with FMH, indicating that it was due to histamine formed by decarboxylation of L-histidine in the central nervous system. The anticonvulsive effect of L-histidine was also reduced by the H1-antagonist pyrilamine, but not by the H2-antagonist zolantidine, indicating that the effect on electrically-induced seizure is mediated through central H1-receptors. Metoprine, which increased the histamine levels in the cerebral cortex, diencephalon and midbrain of mice, decreased the duration of clonic convulsions dose-dependently. Conversely, FMH, which decreased the brain histamine levels, increased the duration of clonic convulsions. Good inverse correlations were found between the duration of clonic convulsions and brain histamine levels, especially in the diencephalon: the histamine levels were inversely proportional to the duration of clonic convulsions. No correlation was found between the duration of tonic convulsions and brain histamine levels. These results suggest that the histaminergic neuron system is important in inhibition of the duration of clonic convulsion on electrically induced seizure in mice.

Selective antagonism of acute ethanol-induced motor disturbances by centrally administered Ro 15-4513 in mice

Results of the present investigation demonstrated that Ro 15-4513 when given ICV selectively antagonized ethanol-induced motor distrubances at doses that did not produce motor incoordination and lacked proconvulsant activity. Ro 15-4513 in 10-, 15-, and 22-ng doses antagonized, roughly in a dose-dependent manner, ethanol-induced motor incoordination. The 10-ng dose produced an optimal effect with nearly complete antagonism within 30 min postethanol. The higher, 15 and 22 ng, doses of Ro 15-4513 antagonized, as well as probably reversed, ethanol-induced motor incoordination. The stimulation and inhibition of spontaneous motor activity by 1 and 2 g/kg IP ethanol, respectively, were also selectively antagonized by Ro 15-4513. Neither an alteration in the latency and/or duration of pentylenetetrazol-induced convulsions nor an antagonism to sodium pentobarbital-induced motor incoordination and inhibition of spontaneous motor activity by Ro 15-4513 at dose levels that showed antiethanol effects were observed. Only the 150-ng dose of Ro 15-4513, which exhibited intrinsic activity as proconvulsant, attenuated sodium pentobarbital-induced motor incoordination. When given alone at doses higher than those used in motor coordination experiments, Ro 15-4513 markedly increased spontaneous motor activity dose dependently.

Effects of Acute Administration of Nicotine on Convulsive Movements and Blood Levels of Corticosterone in Old Rats

The convulsive movements, blood levels of corticosterone and pharmacokinetics of nicotine after an acute intraperitoneal injection of nicotine (5 mg/kg) were examined in young (6-week-old) and old (2-year-old) rats. In pharmacokinetic study, blood nicotine levels during the elimination phase were significantly higher in old rats than in young rats. However, the duration of convulsions and the elevation of corticosterone levels after the nicotine injection showed significant decreases in old rats compared with those in young rats. These differences of nicotine-induced responses between young and old rats may be involved in the decrease in nicotine sensitivity.

Aggravation of Penicillin-Induced Epilepsy in Rats with Locus Ceruleus Lesions

The rate and pattern of development of seizures induced by penicillin injected intraperitoneally were determined in rats that had been depleted of brain norepinephrine (NE) by bilateral injections of the neurotoxin 6-OH dopamine into the locus ceruleus. Behavioral observations and scalp electrographic recordings were made after injection and the efficacy of NE depletion was determined by high performance liquid chromatography measurement of cortical levels of NE and its metabolites. We found that in comparison to sham-operated control rats, NE-depleted rats had a significantly shorter latency to first observable myoclonic jerk, the first epileptic discharge, the first convulsion with sustained epileptic discharges, and a longer duration of convulsions. We observed a similar electrographic pattern of multifocal spikes with bilateral synchrony in both groups. However, more of the control rats (six of 12) had convulsions as compared to the lesioned rats (four of 12). These findings are consistent with previous evidence that depletion of neocortical NE facilitates the development of epileptiform activity in the CNS; however, a convulsive state was not induced by NE depletion.

Changes in the somatosensory evoked potentials and spontaneous electroencephalogram of hens during stunning in argon-induced anoxia

This study examined the time to loss of consciousness in hens during stunning in argon-induced anoxia. Somatosensory evoked potentials (SEPs) and the spontaneous electroencephalogram (EEG) were recorded in 12 culled hens prior to and during stunning in less than 2% oxygen (air displaced by argon). An additional 20 hens were stunned with a similar concentration of oxygen and the time to loss of posture, eye closure, and the onset and duration of clonic and tonic convulsions were recorded. A further 10 hens were immersed in less than 2% oxygen for 15–17 s and their response to comb pinching was tested as soon as they had been transferred to atmospheric air. It is concluded that the birds had not lost the primary response in their SEPs by the time they started convulsing, but the reduction in the amplitude of the SEPs, changes in their spontaneous EEG and a negative response to comb pinch before the start of the convulsions indicated that the birds were unconscious when they convulsed.

The influence of stress on convulsive parameters in the mouse

Mice exposed to the stress of conspecific aggression for 10 min showed shorter latencies to convulsions induced by pentylenetetrazol but not by pilocarpine. This effect was short lived and was not influenced by pretreatment with naltrexone (5 mg/kg, SC). The onset of pilocarpine-induced convulsions in stressed mice was reduced by the opioid antagonist. Aggression stress did not change the incidence, duration or severity of convulsions triggered by the chemoconvulsants or electroshock. The results differ widely from those obtained using other stressogenic models such as cold-restraint or swim stress. This suggests that alterations of convulsive parameters and the involvement of opioid mechanisms in their mediation are critically dependent on the characteristics of the stressogenic procedure employed.

Changes in the duration of postdecapitation convulsions mediated by adrenergic and serotonergic receptors in the rat

Changes in the duration of postdecapitation convulsions mediated by adrenergic and serotonergic receptors in the rat

Effects of isofloxythepin enantiomers on prolactin secretion and postdecapitation convulsions in rats

Racemic isofloxythepin and its enantiomers (0.05–1.0 mg/kg) administered subcutaneously increased serum prolactin levels in a dose-dependent manner in rats. The potencies of the drugs were equal for this variable. They (0.05–1.0 mg/kg, SC) also decreased dose-dependently the incidence and duration of postdecapitation convulsions, the convulsions being abolished at 1.0 mg/kg in all groups. Although (−)-enantiomer had slightly stronger effects than those of raceme and (+)-enantiomer, there were no great differences in their inhibitory effects on postdecapitation convulsions. The results indicate that isofloxythepin enantiomers in addition to raceme increase serum prolactin levels and inhibit postdecapitation convulsions and that they seem to have similar potency in blocking of dopamine receptors and α 1-adrenoceptors.

Inhibition of post-decapitation convulsions in the rat by dibenzothiepin neuroleptics via [formula omitted] blockade

The mechanisms involved in inhibitory effects of isofloxythepin, a newly synthesized dibenzothiepin neuroleptic, on post-decapitation convulsions were studied in rats. Isofloxythepin (0.05–2.0 mg/kg s.c.) inhibited post-decapitation convulsions in a dose-dependent manner as shown by the decrease in the incidence and the shortening of the duration of convulsions. The convulsions were also inhibited by oxyprothepin, zotepine or chlorpromazine but not by haloperidol. Prazosin and bunazosin, both α 1- adrenoceptor adrenhoceptor, suppressed the post-decapitation convulsions but a non-selective α-adrenoceptor antagonist, tolazoline, was without effect. The convulsions were inhibited dose dependently by clonidine, an α 2- adrenoceptor agonist, but were prolonged in duration by yohimbine, an α 2- adrenoceptor antagonist. Yohimbine antagonized the inhibitory effects of isofloxythepin, prazosin and clonidine. The noradrenaline-induced contraction of rat vas deferens was inhibited by isofloxythepin, prazosin or chlorpromazine. Isofloxythepin bound to α 1- receptors as did chlorpromazine in the rat brain cortex. The results imply that post-decapitation convulsions seem to be inhibited by a block of postsynaptic α 1- adrenoceptors , enhanced by a block of presynaptic α 2- adrenoceptors and reduced by isofloxythepinvia the blocking of postsynaptic α 1- adrenoceptors . The convulsions thus could serve as a good model for studying the actions of drugs on the central nervous system α-adrenoceptors.

Prevention of the convulsant and hyperalgesic action of strychine by intrathecal glycine and related amino acids

Intrathecal administration of 25 μg strychnine induced consistent sensory and motor behavioral events in rats. Sensory events included scratching and biting the lower half of the body, spontaneous vocalizations and skin hyperalgesia, evidenced by vocalization and reflex scratching in response to stimulation with a 5.5 g von Frev fiber. This mild stimulus failed to elicit vocalizations in the preinjection condition. Strychnine induced two types of motor seizures: (1) falling over with tail whipping and (2) convulsions. The effect of equimolar doses of glycine ( G) and some related amino acids: β-alanine ( A), taurine ( T) and betaine ( B) on the strychnine syndrome was tested by administering them (intrathecal route) along with strychnine. T and G but not B significantly decreased most of the sensory events triggered by strychnine. All amino acids significantly decreased the incidence and duration of convulsions; T and B abolished them. A decreased vocalizations and skin hyperalgesia but synergized with strychnine to facilitate scratching and self biting. These results are consistent with findings that G, A and T displace strychnine from its binding sites in the CNS.

Anti-convulsant effects by reduced glutathione and related aminoacids in rats treated with isoniazid

Rats were treated with different doses of isoniazid (INH) causing convulsions. Lethal dose (DL 50) and effective convulsant dose (ED 50) were calculated. Reduced glutathione (GSH) and related aminoacids were administered to rats receiving INH: the latency and duration of convulsions were recorded; cerebral gamma-aminobutyric acid (GABA) concentrations were determined in rats receiving INH and an association of GSH and INH. GSH and its related aminoacids as cysteine and glycine greatly decreased the duration of INH-induced seizures, while glutamic acid did not protect against convulsions caused by INH. Furthermore, INH causes a decrease in cerebral GABA levels to about half and GSH repeated pretreatment did, however, not prevent the INH induced decline of GABA content: hence, the anti-convulsant effect of GSH can not be ascribed to the restoration of normal levels of anti-epilectically acting GABA, but can be attributed to cysteine and glycine, aminoacids linked to GSH.

Inhibition of sound-induced convulsions by metoprine in the audiogenic seizure susceptible rat.

Metoprine which increases brain histamine by blocking its methylation, was recently demonstrated to inhibit electrically induced tonic convulsions in rats. Its effect was now tested on audiogenic convulsions in genetically audiogenic seizure sensitive rats. Metoprine (20 mg/kg, i.p.) reduced the severity of seizures significantly 4 and 28 h after drug administration. Also the duration of convulsions was significantly decreased. These results agree with an involvement of histaminergic neurons in convulsive phenomena perhaps as a part of an anticonvulsive inhibitory transmitter system.

5-Hydroxytryptamine antagonists and the 5-methoxy-N,N-dimethyltryptamine-induced changes of postdecapitation convulsions.

The ability of various compounds to antagonise the 5-MeODMT induced prolongations of latency and duration of postdecapitation convulsions (PDCs) were compared. The 5-hydroxytryptamine (5-HT) receptor antagonists, mianserin, methergoline, cinanserin and methysergide antagonised the 5-MeODMT (0.5 to 4.0 mg/kg) induced prolongations of latency to onset of convulsions substantially and to a lesser extent the prolongation of duration. The efficacy of the 5-HT antagonists for blocking 5-MeODMT changes of PDCs was roughly of the order mianserin greater than cinanserin greater than methysergide greater than methergoline. Pirenperone, the 5-HT2 antagonist, and pimozide, the dopamine receptor antagonist did not antagonise the 5-MeODMT induced changes. Mianserin, methergoline, cinanserin and methysergide, by themselves, prolonged the duration of PDCs but did not affect latency. Pirenperone (0.25 mg/kg) prolonged both the latency and duration of the PDCs while pimozide (0.5-2.0 mg/kg) had no effect upon PDCs. This evidence suggests that 5-MeODMT induced changes of PDCs are mediated via 5-HT1 receptors and thus a reliable model to combine with other measures of spinal function is suggested.

Effects of adrenalectomy and hypophysectomy on postictal seizure protection

Endogenous opioid systems activated by seizures appear to contribute to the postictal inhibition of subsequent seizure activity. In consideration of the possible postictal anticonvulsant actions of endogenous opioids of peripheral origin, we examined whether intact adrenal or pituitary sources of these opioids are necessary for the progressive decline in convulsion intensity and duration normally recorded during a series of 6 intermittent maximal electroshocks (MES). Adrenalectomy did not alter the progressive seizure protection associated with repeated MES. Hypophysectomy, in contrast, increased convulsion duration and abolished progressive reductions in convulsion severity. These data indicate that: (1) adrenal secretions do not substantially contribute to postictal protective mechanisms, and (2) endogenous opioids of pituitary origin may be involved in postictal protective mechanisms.

Effects of new neuroleptics, isofloxythepin and zotepine, on post-decapitation convulsions and prolactin secretion in rats

Oral administration of isofloxythepin (0.5–8.0 mg/kg) inhibited decapitation convulsions in a dose-dependent manner as shown by decreasing the incidence and shortening the convulsion's duration, the effects continuing until 24 hr after administration. Zotepine (8, 16 mg/kg, SC) also decreased the duration but not the incidence of the convulsion. However, the other neuroleptics such as haloperidol, spiperone, perphenazine, trifluoperazine, pimozide and sulpiride failed to affect decapitation convulsions. Reserpine (8 mg/kg, SC) inhibited decapitation convulsions, accompanied by decreasing levels of norepinephrine, dopamine and serotonin in the spinal cord. Isofloxythepin at doses of 4 and 8 mg/kg, PO which completely abolished decapitation convulsions, failed to change norepinephrine and dopamine levels but increased serotonin levels in the spinal cord. Isofloxythepin (0.5–8.0 mg/kg) increased serum prolactin levels in a dose-dependent manner and zotepine (16 mg/kg), haloperidol (1 mg/kg) and reserpine (8 mg/kg) also elevated the levels. The results imply that both isofloxythepin and zotepine, but not the other neuroleptics, inhibit convulsions without decreasing spinal levels of norepinephrine which appears to be the amine most directly involved in the occurence of decapitation convulsions, although these neuroleptics enhance prolactin secretion by blocking dopamine receptors in the pituitary.