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

The effect of antagonists of serotonin (5-HT) receptor subtypes and alpha 2-adrenoceptors was investigated on audiogenic seizures and locomotor activity in DBA/2 mice. 5HT1c receptor antagonists (mianserin and cyproheptadine), 5-HT3 receptor antagonist (zacopride) and 5-HT4 receptor antagonist (ICS 205-930) increased the latency of audiogenic seizures and decreased the severity of convulsions in young (20-27 days old) DBA/2 mice. However, the effect of these antagonists varied in older (30-37 days old) mice. Ketanserin, 5-HT2 receptor antagonist, was devoid of any activity on audiogenic seizures. Yohimbine (0.5 mg/kg, i.p.), an alpha 2-adrenoceptor antagonist, increased the severity of audiogenic seizures, and the anti-convulsant effect of 5-HT receptor subtypes antagonists became more pronounced in the presence of yohimbine. 5-HT3 and 5-HT4 receptor antagonists produced hypolocomotor activity in young mice whereas 5-HT1c and 5-HT2 receptor antagonists were devoid of any effect on locomotor activity. Yohimbine did not induce any effect on locomotor activity but the mice exhibited more pronounced hypolocomotor activity following the administration of 5-HT3, 5-HT4 and 5HT1c receptor antagonists in the presence of yohimbine. However, the results varied with these agents in the older mice. These observations implicate a role of 5-HT1c, 5-HT3, 5-HT4 and alpha 2-adrenoceptors in audiogenic seizures in young DBA/2 mice, and 5-HT3 and 5-HT4 receptors in locomotor activity in these mice. Furthermore, these results also suggest an interaction between 5-HT receptors and alpha 2-adrenoceptors, and differential development patterns of various 5-HT receptor subtypes in the CNS.
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PMID:Effects of 5-HT receptor antagonists on seizure susceptibility and locomotor activity in DBA/2 mice. 139 77

Pharmacological studies were undertaken to clarify the profile of cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) butyl) hexahydro-1H-isoindole-1,3-(2H)-dione hydrochloride (SM-9018), a new neuroleptic drug. SM-9018 had very high binding affinities for both 5-hydroxytryptamine2 (5-HT2) and dopamine2 (D2) receptors, unlike many other neuroleptics. SM-9018 also strongly inhibited 5-HT2 receptor-mediated behavior such as tryptamine-induced clonic seizure and D2 receptor-mediated behavior such as methamphetamine-induced hyperactivity, apomorphine-induced stereotypy and climbing behavior. SM-9018 possessed only a weak cataleptogenic activity, which may be clinically related to extrapyramidal side effects, despite its potent D2 antagonistic activity. Moreover, SM-9018 induced weak central depressant effects such as inhibition of spontaneous locomotor activity and motor coordination, as compared with classical neuroleptics (haloperidol and chlorpromazine). These results suggest that SM-9018 is a new neuroleptic drug with both potent 5-HT2 and D2 antagonistic activities and with low cataleptogenic and central depressant activities.
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PMID:Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5-hydroxytryptamine2 and dopamine2 antagonistic actions. 197 78

Abnormal function of serotonergic neurones may be involved in the age-related susceptibility of DBA/2J mice to generalised convulsions induced by auditory stimulation. We have measured 5-HT2 receptor binding sites and synaptosomal 5-HT uptake in 5 brain regions of DBA/2J mice at ages before, during and after their maximal susceptibility to audiogenic seizures and in age-matched C57 B1/6 mice, a strain resistant to audiogenic seizures at all ages. The number of 5-HT2 binding sites was 20% higher in the cerebral cortex of DBA/2J than C57 B1/6 mice at the time of maximal susceptibility of DBA/2J mice to audiogenic seizures but did not differ at other ages. The number of 5-HT2 binding sites did not differ between the two strains at the ages studied in forebrain, mid-brain, hippocampus and pons-medulla. A marked reduction in the number of 5-HT2 binding sites was apparent in the mid-brain, hippocampus and pons-medulla of both strains of mice between 13-15 days of age and 21-23 days of age. Synaptosomal 5-HT uptake did not differ significantly between DBA/2J and C57 B1/6 in any of the brain regions at the ages studied. The higher density of cortical 5-HT2 binding sites in DBA/2J mice may contribute to their susceptibility to sound-induced seizures.
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PMID:5-HT2 receptor binding and 5-HT uptake in mouse brain: developmental changes and the relationship to audiogenic seizure susceptibility in DBA/2J mice. 271 83

Dotarizine (DOT), a compound performing both as calcium antagonist and as 5-HT2 receptor antagonist, was evaluated for its ability to protect against electroconvulsive shock (ECS)- and pentylenetetrazol (PTZ)-induced performance deficit in a passive avoidance "step-down" task in rats. Its effect on electric and PTZ seizure models was also studied. DOT administered orally at a dose of 50 mg/kg for 5 days before learning had no significant effect on retention tests given 3 h, 24 h and 7 days after the training session. It should be noted, however, that DOT completely prevented ECS- and PTZ-induced amnesia in passive avoidance situation. DOT had a pronounced protective effect against electric seizures but did not affect PTZ seizures. The present results provide additional evidence for the role of serotonergic neurotransmitter system and calcium homeostasis for memory and seizure reactivity and may be important in the development of effective treatment strategies for memory dysfunction.
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PMID:Effect of dotarizine on electroconvulsive shock or pentylenetetrazol-induced amnesia and on seizure reactivity in rats. 762 21

In this study we addressed the effects of the 5-HT2 receptor antagonist sertindole in rats. The compound was administered in doses of 0.08, 0.32, and 1.28 mg/kg, whereas a control group received the solvent. The effects of sertindole on sleep-wake states, behavioral patterns, and background electroencephalogram were studied. Following injection of drug or solvent, we recorded the electroencephalogram and electromyogram for two periods of 4 h in the dark period of the light-dark cycle on 2 successive days. On the 1st day sertindole induced a significant increase in deep slow-wave sleep, but only with a dose of 0.32 mg/kg. Furthermore, a decrease in REM sleep in all three drug groups was established. The suppression of REM sleep was still present on the 2nd day. Sertindole also induced a decrease in alternation between behavioral patterns on the 1st day. There were no significant changes in the spectral content of the background electroencephalogram. In a parallel experiment it appeared that sertindole had no main effects on epileptic spike-wave discharges. This was established with a dose of 1.28 mg/kg sertindole in rats with absence seizures. These findings suggest that sertindole, similar to other compounds modulating 5-HT2 receptors, influences sleep-wake states in rats by decreasing REM sleep and mildly increasing deep slow-wave sleep, whereas behavioral variation is slightly diminished, with no effects on the background EEG and almost no effects on spike-wave discharges.
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PMID:Effects of sertindole on sleep-wake states, electroencephalogram, behavioral patterns, and epileptic activity of rats. 766 52

Ethanol-dependent mice were treated with the 5-HT3 antagonist MDL 72222 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10, and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose-dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after withdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display any seizures. Treatment with another 5-HT3 antagonist, ICS 205-930 (23 and 46 mg/kg), or the 5-HT2 receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure.
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PMID:The 5-HT3 antagonist MDL-72222 exacerbates ethanol withdrawal seizures in mice. 804 47

Based on our previous findings that a serotonin (5-HT) precursor L-5-hydroxytryptophan and a 5-HT1 a receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin can suppress seizures kindled from the feline hippocampus (HIP), we have suggested that 5-HT1 a receptors play an inhibitory role in HIP seizure generation. In order to clarify the role of 5-HT2 receptors in epilepsy, the present study examined the effects of a 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane(DOI) and a 5-HT2 receptor antagonist ketanserin on HIP-kindled seizures. Following the completion of HIP kindling, five cats received intravenous injections of 0.9% saline, DOI (1.0mg/kg) or ketanserin (1.0mg/kg). Electrical stimulation at the generalized seizure triggering threshold was delivered to the kindled HIP 15 min after drug administration. The anticonvulsant effects were assessed by the behavioral seizure stage, afterdischarge duration, latency to the onset of stages 4 and 6, and duration of a generalized tonic-clonic convulsion (GTC). Although no significant change was found in the seizure stage following the administration of either drug, both DOI and ketanserin significantly altered the latency for seizure generalization. DOI significantly reduced the latency to the onset of stage 6 GTC as compared with saline, with a significant reduction in the afterdischarge duration. In contrast, ketanserin significantly increased the latency to the GTC onset as compared with saline. Neither the latency of the stage 4 onset nor the GTC duration was significantly affected by these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Serotonergic mechanisms of hippocampal kindled seizures in cats--effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and ketanserin]. 826 33

The present study examines the influence of electroconvulsive seizure (ECS), as well as antidepressant drugs, on levels of serotonin2 (5-HT2) receptor mRNA in rat frontal cortex. Using a sensitive RNase protective assay, preliminary studies demonstrated the predicted regional distribution for the 5-HT2 receptor mRNA: levels of 5-HT2 mRNA were highest in frontal cortex (2.58 amol/micrograms of total RNA), intermediate in neostriatum, thalamus, and midbrain, and lowest in hippocampus, cerebellum, and choroid plexus. Chronic (10 or 14 days), but not acute (1 or 3 days), ECS treatment significantly increased levels of 5-HT2 receptor mRNA. ECS treatment resulted in a similar time-dependent up-regulation of 5-HT2 receptor ligand binding; chronic, but not acute, ECS treatment significantly increased levels of [3H]ketanserin ligand binding, confirming previous reports. Northern blot analysis demonstrated that 5-HT2 receptor mRNA occurs as two bands (approximately 5 and 6 kb in size), both of which were increased by chronic ECS treatment. The influence of antidepressant drug treatments on 5-HT2 receptor mRNA was also examined. Chronic fluoxetine treatment increased levels of 5-HT2 receptor mRNA, although levels of [3H]ketanserin ligand binding were not altered. In contrast, chronic administration of imipramine, mianserin, and tranylcypromine, treatments that decreased ligand binding, did not decrease levels of 5-HT2 receptor mRNA. In fact, mianserin treatment caused a small, but significant, increase in levels of receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic electroconvulsive seizures increase the expression of serotonin2 receptor mRNA in rat frontal cortex. 837 84

(R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045), a novel thiazole derivative, has high affinities for the human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 2.54, 0.55 and 0.54 nM, respectively. NRA0045 is approximately 91-fold more potent at the dopamine D4.2 receptor, compared with human cloned dopamine D2L receptor. NRA0045 also has high affinities for the serotonin (5-HT)2A receptor (Ki = 1.92 nM) and alpha-1 adrenoceptor (Ki = 1.40 nM) but weak affinities (IC50 values are approximately 1 microM) for six other neurotransmitter receptors (adenosine1, 5-HT1A, 5-HT1C, dopamine transporter, alpha2A and alpha2A) and negligible affinities (IC50 values are over 10(-5) M) for 42 other receptors, including neurotransmitters and hormones, ion channels and second messenger systems. Locomotor hyperactivity induced by methamphetamine (1 mg/kg i.p.) in mice was dose-dependently antagonized by NRA0045 (ED50 = 0.5 mg/kg i.p. and 1.9 mg/kg p.o., respectively). Methamphetamine (10 mg/kg i.p.)-induced stereotyped behavior in mice was dose-dependently antagonized by NRA0045, whereas NRA0045 did not exceed 50% inhibition even at the highest dose given (30 mg/kg i.p.). Catalepsy was dose-dependently and significantly induced by NRA0045 in rats, whereas NRA0045 did not exceed 50% induction even at the highest dose given (30 mg/kg i.p.). Thus NRA0045 blocks behaviors associated with activation of the mesolimbic/mesocortical dopaminergic neurons more selectively than behaviors associated with nigrostriatal dopaminergic neurons. In rats, tryptamine-induced clonic seizure, a 5-HT2 receptor-mediated behavior, was also dose-dependently inhibited by NRA0045 (ED50 = 1.7 mg/kg i.p.). Norepinephrine-induced lethality is regarded as being induced through the alpha-1 adrenoceptor. NRA0045 dose-dependently antagonized norepinephrine-induced lethality in rats (ED50 = 0.2 mg/kg i.p.). Thus NRA0045 may have a unique antipsychotic activity with regard to dopamine D4 and 5-HT2A receptors and alpha-1 adrenoceptor antagonistic activities, without producing the extrapyramidal side effects.
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PMID:In vitro and in vivo characterization of the dopamine D4 receptor, serotonin 5-HT2A receptor and alpha-1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045). 922 39

Crinum glaucum A. Chev (Amaryllidaceae) (CG) is a bulbous plant widely used in folk medicine in the treatment of cough, asthma and convulsions. This study was carried out to investigate the anticonvulsant, anxiolytic and hypnotic effects of the aqueous bulb extract of C. glaucum and its possible mechanism (s) of action. The anticonvulsant activity of C. glaucum extract (400-1200 mg kg(-1) p.o.) was investigated using picrotoxin, strychnine, isoniazid, pentylenetetrazol and N-methyl-D-aspartate (NMDA)-induced seizures in mice while the elevated plus maze test (EPM) and hexobarbitone-induced sleeping time (HIST) were used to evaluate the anxiolytic and hypnotic effects, respectively. Animals were pretreated with flumazenil (3 mg kg(-1); i.p. GABA(A) receptor antagonist), cyproheptadine (4 mg kg(-1); i.p. 5-HT2 receptor antagonist), L-arginine (500 mg kg(-1); p.o. Nitric Oxide (NO) precursor) and L-Nitroarginine (L-NNA) (10 mg kg(-1) i.p. Nitric Oxide Synthase (NOS) inhibitor) were used to investigate the probable mechanism (s) of anticonvulsant activity. Oral administration of CG significantly (p < 0.001) delayed the onset of seizures induced by picrotoxin, strychnine, isoniazid and pentylenetetrazol with peak effect at 1200 mg kg(-1) in comparison to control groups. CG (800 and 1200 mg kg(-1)) strongly antagonized NMDA-induced turning behavior. Pretreatment of mice with cyproheptadine could not reverse the anticonvulsant effect of CG. However, pretreatment with flumazenil and L-NNA significantly (p < 0.05) reversed the anticonvulsant effect of CG while L-arginine pretreatment significantly (p < 0.001) delayed the onset of seizures when compared with control and extract (1200 mg kg(-1) only). CG potentiated hexobarbitone-induced sleeping time with peak effect at 400 mg kg(-1) and also significantly (p < 0.05) increased open arm exploration in EPM and had its peak anxiolytic effect at 100 mg kg(-1). The data obtained suggests that aqueous bulb extract of Crinum glaucum possess anticonvulsant, anxiolytic and hypnotic activities which involve an interaction with GABAergic, nitrergic and glutaminergic systems to exert its effects.
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PMID:Anticonvulsant, anxiolytic and hypnotic effects of aqueous bulb extract of Crinum glaucum A. chev (Amaryllidaceae): role of GABAergic and nitrergic systems. 2450 97


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