Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Derivatives of ethyl-beta-carboline-3-carboxylate, ZK 91296, ZK 93423 and ZK 95962 have potent anticonvulsant activity against sound-induced seizures in audiogenic DBA/2 mice and against photically-induced seizures in the baboon, Papio papio. The convulsant beta-carbolines, DMCM and beta-CCM, have proconvulsant and convulsant activity in the same animal models. DMCM and beta-CCM are similar in potency as convulsants in DBA/2 mice (ED50 value for DMCM: 1.3 mg/kg; ED50 value for beta-CCM; 0.8 mg/kg), but differ with respect to their profiles for protection by anticonvulsant drugs. The anticonvulsant potencies of diazepam and clobazam are similar against both types of beta-carboline-induced seizures, whereas quazepam protects better against beta-CCM seizures (4 fold elevation in ED50 value at 1 mg/kg quazepam IP) than against DMCM seizures (1.7 fold elevation in ED50 value), supporting a preferential action of beta-CCM on BZ1 receptors. Valproate (400 mg/kg) and gamma-vinyl-GABA (1.5 g/kg) protect better against beta-CCM seizures (9.5 and 5.9 fold elevations in ED50 values respectively) than against DMCM seizures (1.8 and 2.7 fold elevations in ED50 values respectively). The excitatory amino acid antagonist, 2-amino-7-phosphonoheptanoic acid, has significant anticonvulsant activity against DMCM seizures. The elevated regional GABA levels in brains of DBA/2 mice observed during beta-CCM seizures are eliminated by the pretreatment with Ro 15-1788, which also blocks the seizure activity.
 ...
PMID:Bidirectional effects of beta-carbolines in reflex epilepsy. 311 61

Tolerance to nicotine occurs in mice after its chronic administration. This tolerance is accompanied by an up-regulation of nicotinic receptors as assessed by the binding of (3H)-nicotine and alpha-(125I)-bungarotoxin (BTX). Past studies (Marks et al. 1983, 1986) have shown that the increase in BTX binding sites is most evident in the hippocampus. Mice that have a greater concentration of BTX binding sites in the hippocampus are more sensitive to the convulsant effects of nicotine (Miner et al. 1984, 1985, 1986). In the study reported here, mice from the DBA/2Ibg strain, which are relatively resistant to nicotine-induced seizures and have a relatively low concentration of hippocampal BTX binding sites (Miner et al. 1984), were infused with nicotine for 10 days. At various time points after cessation of nicotine administration, sensitivity to the convulsant effects of nicotine was assessed. Mice were then sacrificed and BTX binding was determined in three regions: cortex, midbrain, and hippocampus. As expected, chronic treatment with nicotine resulted in a significant up-regulation of BTX binding sites in the hippocampus. Chronic nicotine treatment also produced significant tolerance to nicotine-induced seizures. Hippocampal BTX binding sites returned to control levels within 2 days after stopping nicotine infusion, whereas tolerance was not lost until 5 days. These results suggest that factors other than the number of hippocampal BTX binding sites affect nicotine-induced seizure sensitivity, at least following chronic nicotine treatment.
 ...
PMID:The effect of chronic nicotine treatment on nicotine-induced seizures. 313

The anticonvulsant activity of avermectin B (AVM) was studied after systemic administration in DBA/2 mice (seizures induced by sound) and rats (seizures induced by pentylenetetrazol, cephazolin and maximal electroshock test). Protection against sound-induced seizures was given after intraperitoneal administration of AVM (30 and 50 mg/kg). Cephazolin-induced seizures in rats were attenuated by intraperitoneal administration of AVM (10 and 20 mg/kg). AVM increased the antipentylenetetrazol activity of diazepam. No significant protection against the tonic component in the electroshock test was observed. Behavioural effects of AVM included signs of sedation in both mice and rats. In all, these results indicate that, besides its specific anthelmintic effects, AVM possesses anticonvulsant properties, the mechanism(s) of which still remain to be elucidated.
 ...
PMID:Anticonvulsant effects of avermectin in DBA/2 mice and rat. 326 24

Convulsive dose 50s (CD50s) for various convulsive drugs and minimal and maximal electroshock seizure thresholds were determined in DBA and C57 mice. DBA mice had lower maximal electroshock seizure thresholds (MESTs, 15%) and CD50s for homocysteine thiolactone (HTL, 23%) and bicuculline (69%), and a higher CD50 for pentylenetetrazol (PTZ) at 3 weeks of age, the age of maximal audiogenic seizure (AGS) susceptibility. At 8 weeks, when DBA mice are not susceptible to AGSs, significant differences were a lower minimal electroshock seizure threshold (mEST, 37%) and maximal EST (MEST) (19%), lower CD50s for N-methyl-D-aspartate (NMDA) (39%), kainic acid (KA, 50%), HTL (32%), strychnine (37%), and a higher CD50 for nicotine (55%) in DBA mice. Based on these data it is suggested that pathways involving NMDA and KA receptors are responsible for increased susceptibility to seizure initiation (mEST), and are opposed by glycine pathways, and that opposing GABA and cholinergic systems at higher CNS levels are involved in seizure spread (AGSs and MEST) in these mice. Latency patterns indicate that nicotine, strychnine, PTZ and bicuculline have high blood-brain barrier (BBB) penetrability. Picrotoxin and the excitatory amino acid receptor agonists had longer latencies, suggesting low BBB penetrability. Age-related changes in latency, however, give evidence that difficulty in drug penetration of the BBB is not responsible for differences observed in CD50s between strains.
 ...
PMID:Seizure susceptibility in DBA and C57 mice: the effects of various convulsants. 329 31

CPP has a potent anticonvulsant effect against sound-induced seizures in audiogenic DBA/2 mice. Pretreatment with CPP (0.01-10 nmol i.c.v., 45 min) protects against successive phases of sound-induced seizures in a dose-dependent fashion (ED50, tonic phase, 0.023 nmol; clonic phase, 0.039 nmol; wild running, 0.17 nmol). Systemic administration of CPP (0.001-0.1 mmol/kg i.p., 45 min) produces a similar protection (ED50, tonic phase, 0.0012 mmol/kg; clonic phase, 0.0026 mmol/kg; wild running, 0.021 mmol/kg). Following the administration of a fully anticonvulsant dose of CPP (0.1 mmol/kg i.p., 45 min) to adult DBA/2 mice regional brain glucose (cerebellum and striatum) levels are elevated and lactate (striatum and hippocampus) levels decrease. The CPP-induced changes in alanine, serine and glycine paralleled those of lactate. Aspartate levels are significantly decreased by CPP in the striatum (-21%) and the hippocampus (-23%).
 ...
PMID:Anticonvulsant action and biochemical effects in DBA/2 mice of CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate), a novel N-methyl-D-aspartate antagonist. 330 90

1. The behavioural and anticonvulsant effects of several drugs acting by various mechanisms on calcium-channels or affecting intracellular Ca2+ concentrations were studied after both systemic and intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB) in animals placed singly under a perspex dome. 3. Flunarizine and dihydropyridine derivatives, belonging to class I of calcium entry blockers, administered intraperitoneally, were the most potent compounds. 4. Diltiazem, a benzothiazepine derivative belonging to class III, and HA 1004, a calcium antagonist, acting by inhibiting Ca2+ mobilization from intracellular stores, injected intraperitoneally, were 3-7.6 fold and 5.8-10.7 fold less potent than flunarizine respectively. 5. Verapamil and methoxyverapamil, two phenylalkylamine derivatives, given intraperitoneally, were completely ineffective in preventing sound-induced seizures in DBA/2 mice. In addition, high doses of verapamil and its methoxyderivative occasionally produced spontaneous tonic-clonic seizures. 6. After intracerebroventricular administration of the hydrosoluble calcium entry blockers, belonging to different classes, the anticonvulsant effects were similar to those observed after systemic administration. 7. The systemic administration of Bay K 8644, a dihydropyridine analogue, having the ability to stimulate calcium entry into cells produced a dose-dependent increase in clonic and tonic convulsions and other neurological side effects. 8. The present results strongly support the idea that some Ca2+ antagonists may be useful in human epilepsy.
 ...
PMID:Anticonvulsant effects of some calcium entry blockers in DBA/2 mice. 335 4

Inactivation of the nicotinic receptor via the process of desensitization has been well characterized for the nicotinic receptor in vitro, but potential behavioral manifestations of desensitization have received little study. To test whether behavioral desensitization occurs, C3H and DBA mice were pretreated with subseizure-producing doses of nicotine and nicotine-induced seizure sensitivity was determined at various time intervals after pretreatment. Fifteen minutes after nicotine pretreatment, DBA mice were significantly less sensitive to nicotine-induced seizures than were saline pretreated mice after both IP and IV administration. Seizure sensitivity returned to baseline levels at 60 minutes after pretreatment for the IP route of administration and at 30 minutes for the IV route of administration. Sensitivity to nicotine-induced seizures was altered for C3H mice under only one experimental condition; 7.5 minutes after IP injection with 2.0 mg/kg nicotine. Thus, DBA mice display a marked behavioral desensitization as a result of nicotine pretreatment whereas C3H mice do not. These results, in conjunction with our previous studies, indicate that nicotine-induced seizure sensitivity may be influenced by a minimum of two factors: the concentration of nicotinic receptors in the brain and possibly the ability of these receptors to inactivate in the presence of nicotine.
 ...
PMID:Effect of nicotine pretreatment on nicotine-induced seizures. 336 31

Differences in resistance to 3-mercaptopropionic acid (MP)-induced seizures exist between DBA/2Ibg and C57BL/6Ibg inbred strains of mice; C57BL/6Ibg mice are more resistant to MP-induced seizures. To determine the mode of inheritance for seizure resistance, a classical genetic analysis was conducted using these two parental strains, their F1, F2, and backcross generations. Latencies to seizure onset and tonus after intraperitoneal (IP) injections of MP (25-40 mg/kg) were quantified. For all populations mean latencies to onset and tonus decreased in a dose dependent manner with the hybrid generations exhibiting a seizure resistant phenotype resembling the C57BL/6Ibg strain. In general, female mice were less resistant to MP-induced seizures than males; however, a significant degree of resistance was retained by the C57BL/6Ibg females and their female progeny. A quantitative assessment of the pattern of inheritance for seizure resistance using a weighted least-squares regression approach indicated that an additive-dominance model explained latency to seizure onset data at 25, 35 and 40 mg/kg. However, at 30 mg/kg, the model required the addition of an epistatic parameter to best describe mean scores at this dose. The results of these analyses suggest that resistance to MP-induced seizures is transmitted in a dominant manner.
 ...
PMID:Classical genetic analysis of GABA-related seizures. 336 43

DBA/2J mice exhibit audiogenic seizure susceptibility (AGSS) and lower electroshock seizure thresholds compared with C57BL/6J mice. Thyroid function, including thyroxine (T4), 3,5,3'-triiodothyronine (T3), and thyrotropin (TSH) concentrations, T4/T3 ratio, and iodide uptake, of DBA and C57 mice were compared. Thyroid function was also assessed in relation to AGSS and severity in DBA mice. DBA mice have a larger thyroidal pool of iodide due to increased iodide uptake and possibly decreased release, but not to an increased organification rate. This increased iodide uptake exists until about 40 days of age. DBA mice also have a decreased radiochloride space and increased thyroid weight, indicative of enhanced TSH activity. The DBA mice show high T4 and TSH concentrations and a high T4/T3 ratio between the ages of 20 and 40 days. Beginning at 40 days of age the DBA mice have high T4, TSH, and T3 concentrations leading to a T4/T3 ratio approximating the C57 ratio. At any age, DBA mice demonstrating clonic/tonic seizures in response to auditory stimulation have hormone concentrations similar to their 21-day-old counterparts with seizures. Mice that show decreased response to auditory stimulation have hormone concentrations similar to the older age group. The increased thyroid activity of DBA mice is the result of enhanced TSH secretion. The increased TSH production is due to adaptations corresponding to the different age and AGSS. A decreased conversion of T4 to T3 by 3,3,5'-monodeiodinase, is responsible for the increase in TSH due to loss of T3 negative feedback on the anterior pituitary gland. By 40 days of age, the Type I 5'-deiodinase matures whereas the brain deiodinase activity remains subnormal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A comparison of thyroid function in DBA/2J and C57BL/6J mice. 340 39

Abnormalities in noradrenaline-mediated neurotransmission have been advocated as a basis of the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured the kinetics of synaptosomal high-affinity noradrenaline uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures, and age-matched C57 BL/6 mice, a strain resistant to audiogenic seizures at all ages. No differences were found between the two strains of mice in any of the brain regions studied. Abnormalities of high-affinity noradrenaline uptake do not contribute to audiogenic seizure susceptibility of DBA/2J mice.
 ...
PMID:Synaptosomal high-affinity noradrenaline uptake does not differ between mice susceptible (DBA/2J) and resistant (C57 BL/6) to audiogenic seizures. 350 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>