Seizure-inducing

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Very high doses of caffeine can induce seizures in those with no preexisting seizure disorder. Caffeine also prolongs seizures induced by electroconvulsive treatment in humans (Shapira et al. 1987). Given the... 

The story of the discovery of pregabalin (2) began in 1991, when Silverman and Taylor published a paper on the anticonvulsant effect of 3-alkyl GABA analogs (Silverman et ah, 1991). Out of this collection of compounds, 3-isobutyl GABA stood out as the most active analog in the series, which protected mice from seizures induced by corneal electroshock. 

Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

Meperidine differs from morphine in that it has far less antitussive effect and little constipative effect. The drug is particularly useful in cancer patients and in pulmonary patients, in whom the cough reflex must remain intact. However, it does have more seizure-inducing activity than morphine. Although meperidine produces spasms of the biliary tract and colon, such spasms are of shorter duration than those produced by morphine. 

Mechanism of tolerance. The molecular events involved in the development of tolerance to carbamazepine have not been clearly identified. However, in a preclinical animal model using amygdala-kindled seizures, S. R. B. Weiss and colleagues (1995) in our laboratory have found that the variety of seizure-induced adaptive changes that usually emerge following seizures fail to do so with development of tolerance to the anticonvulsant effects of carbamazepine. The loss of these adaptive changes, such as increases in... 

Although exploratory rearing and its suppression has some face value as an animal model of mania and its treatment, this behavior has a large variance and is not always replicable. We sought a behavior that would give us a robust and consistent Li effect, which could then be modified by administering inositol intracerebroventricularly. We examined the effect of inositol on limbic seizures induced by Li -pilocarpine [Kofman et al. 1993]. We first... 

Recently, a method for TMS of the brain has been developed. By using TMS it is possible to noninvasively depolarize neurons located deep in the brain without induction of seizures or pain. Thus, it may be possible to compare behavioral effects of TMS and known effects of repeated ECS and other antidepressants in rats. ECS reverses behavioral despair in the swim test and enhances apomorphine hyperactivity and stereotypy. TMS appears to have similar effects to ECS on reversal of the despair in the swim test. Rapid [25-Hz] TMS but not slow (0.2-Hz) TMS potentiated apomorphine stereotypy. ECS is followed by a postictal inhibitory period for further seizures. In this study, TMS as well as ECS increased the seizure threshold for subsequent stimulation and decreased the duration of subsequent seizure. Rapid [25-Hz] TMS but not slow [5- or 1-Hz) TMS decreases the duration of seizure induced by electrical current. 

Herberg LJ, Watkins PJ Epileptiform seizures induced by hypothalamic stimulation in the rat, resistance to fits following fits. Nature 209 515-516, 1966 Herberg LJ, Tress KH, Blundell JE Raising the threshold in experimental epilepsy by hypothalamic and septal stimulation and by audiogenic seizures. Brain 92 313-328, 1969... 

Terry JB, Padzernik TL, Nelson SR Effect of liCl pretreatment on cholinomimetic-induced seizures and seizure-induced brain edema in rats. Neurosci Lett 114 123-127, 1990... 

Breier A, Charney DS, Nelson CJ. Seizures induced by abrupt discontinuation of alprazolam. Am J Psychiatry 1984 141 1606-1607. 

Levetiracetam is a piracetam analog that is ineffective against seizures induced by maximum electroshock or pentylenetetrazol but has prominent activity in the kindling model. This is the first major drug with this unusual preclinical profile that is effective against partial seizures. 

Seizures induced by local anesthetics are usually treated with intravenous anesthetic drugs (eg, thiopental 1-2 mg/kg, propofol 0.5-1 mg/kg, midazolam 0.03-0.06 mg/kg). The muscular manifestations of a seizure can be blocked using a short-acting neuromuscular relaxant drug (eg, succinylcholine, 0.25-0.5 mg/kg IV). It should be emphasized that succinylcholine does not alter the CNS manifestations of local anesthetic-induced seizure activity. Rapid tracheal intubation can prevent pulmonary aspiration of gastric contents and facilitate hyperventilation. 

Akaike et al. have examined the neuroprotective properties of serofendic acid, a substance isolated from serum. The compound was found to protect neuronal cells from both glutamate and NO. This was attributed to the scavenging of OH radicals (from the decomposition of ONOO-) rather than NO itself.320 Indeed, Ueda and colleagues have demonstrated the formation of both NO and OH in neuronal cells upon stimulation of the NMDA receptor.321 These workers also trapped lipid radicals in the brains of rats undergoing seizures induced by the stimulation of a subset of glutamate receptors with kainic acid. Polyphenols have been shown to exacerbate the neurotoxicity of NO.322... 

Kotloski, R., Lynch, M., Lauersdorf, S., Sutula, T. (2002) Repeated brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog Brain Res. 135, 95-110. 

Akaboshi S, Takeshita K. A case of atypical absence seizures induced by leuprohde acetate. Pediatr Neurol 2000 23(3) 266-8. 

Gall C. (1988). Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. J. Neurosci. 8 1852-1862. 

Hashimoto K., Watanabe K., Nishimura T., Iyo M., Shirayama Y., and Minabe Y. (1998). Behavioral changes and expression of heat shock protein hsp-70 mRNA, brain-derived neurotrophic factor mRNA, and cyclooxygenase-2 mRNA in rat brain following seizures induced by systemic administration of kainic acid. Brain Res. 804 212-223. 

Bazan N. G., TuB., and Rodriguez de Turco E. B. (2002). What synaptic lipid signaling tells us about seizure-induced damage and epileptogenesis. In Sutula T. and Pitkanen A. (eds.), Do Seizures Damage the Brain. Perspectives in Analytical Philosophy Elsevier Science BV, Amsterdam, pp. 175-185. 

Liu Z., Stafstrom C. E., Sarkisian M. R., Yang Y., Hori A., Tandon P., and Holmes G. L. (1997). Seizure-induced glutamate release in mature and immature animals an in vivo microdialysis study. NeuroReport 8 2019-2023. 

Lapin I. P., Mirzaev S. M., Ryzov I. V., and Oxenkrug G. F. (1998). Anticonvulsant activity of melatonin against seizures induced by quinolinate, kainate, glutamate, NMDA, and pentylenete-trazole in mice. J. Pineal Res. 24 215-218. 

Meperidine presents a higher risk for seizures than other opioids. Seizures induced by meperidine also tend to be resistant to treatment with opioid antagonists. Therefore, people with a history of seizures, and those at increased risk for first occurrence of a seizure (such as someone with head trauma) should avoid meperidine if possible. Other potential neurological side effects include tremors, delirium, and hallucinations. These side effects are uncommon, but serious. Some people may have an allergic reaction to meperidine, and severe cases can involve respiratory arrest cold, clammy skin generalized weakness and unconsciousness or coma. 

Scharfman, H. E., Goodman, J. H., and Sollas, A. L. (2000). Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells Functional implications of seizure-induced neurogenesis. J. Neurosci. 20, 6144-6158. 

Blockade of the 5-HT7 receptor has been shown to reduce epileptic activity in animal models. Audiogenic seizures induced in DBA/2J mice could be prevented by drugs in a rank order of potency corresponding to their affinity for the 5-HT7 receptor (95). The selective 5-HT7 receptor antagonist SB-258719 has been shown to reduce epileptic activity in an animal model for absence epilepsy, the WAG/Rij rat (65). It is believed to do so by modulating the pacemaker current Ih within the thalamus (96,97). The 5-HT7 receptor has been demonstrated to mediate depolarization within the anterodorsal thalamus by increasing lh through a cAMP-dependent, PKA-independent mechanism (96,97). 

D Hooge, R., Pei, Y.Q., Raes, A., Lebrun, P., vanBogaert, P.P. and Deyn, P.P. de (1 996) Anticonvulsant activity of piperine on seizures induced by excitatory amino acid receptor agonists. Arzneimittel Forschung 46(6), 557-560. 

The leaf essential oil of L. nobilis, which has been used as an antiepileptic remedy in Iranian traditional medicine, was evaluated for anticonvulsant activity against experimental seizures (Sayyah et al., 2002). The essential oil protected mice against tonic seizures induced by maximal electroshock and especially by pentylenetetra-zole. Components responsible for this effect may be methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant doses, the essential oil produced sedation and motor impairment. This effect seems to be related in part to cineol, eugenol and methyleugenol (Sayyah et al., 2002). 

Meldrum, B. S., Horton, R. W., Brierley, J. B. (1974). Epileptic brain damage in adolescent baboons following seizures induced by allylglycine. Brain, 97, 407-418. 

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