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

Pergolide (LY127809, CAS 66104-23-2), a non-selective dopamine agonist, was evaluated for broad behavioral properties in a wide range of pharmacological tests. The selective dopamine2(D2) agonist, bromocriptine, served as a reference standard for those tests where behavioral activity was noted with pergolide. Pergolide and bromocriptine were administered orally to mice at doses of 0.3-30 and 3-300 mg/kg, respectively. Both compounds produced biphasic effects on spontaneous activity, increased hexobarbital-induced sleep time, and lowered mouse body temperature. Qualitative changes with pergolide were observed with some mice showing hyporeactiveness, ptosis, slowed respiration and placing loss. Reserpine-induced hypothermia was reversed by pergolide with significant increases in the body temperature of reserpine-treated mice. However, a further reduction in the body temperature of reserpinized hypothermic mice was seen following bromocriptine administration. Acetic acid-induced writhing and performance on the rotarod were both impaired by higher doses of pergolide. Bromocriptine administration also reduced writhing at higher doses but did not alter performance on the rotarod. Pergolide had no effect on seizure activity as evaluated by electroshock, pentylenetetrazol (pentetrazol) or strychnine. Oxotremorine-induced tremors and salivation, grip strength, and tail-flick were not affected by pergolide. Neither pergolide nor bromocriptine altered established shuttle-avoidance behavior in rats at oral doses of 0.1 to 30 mg/kg. Behavioral assessment of pergolide in dogs was complicated by severe emetic responses at clinically relevant doses greater than 0.003 mg/kg. In summary, these data suggest that pergolide produces a behavioral profile which is characteristic of dopaminergics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral characterization of the new potent nonselective dopamine agonist pergolide. 141 51

The bioavailability and serum level fluctuations of three carbamazepine (CBZ, CAS 298-46-4) slow release preparations marketed in Germany were compared in patients with epilepsy. Ten patients who were on CBZ monotherapy and had reached a steady state with morning trough levels above 10 micrograms/ml received all 3 preparations in sequential 3-day periods. On the 3rd day of each period, a 24-h serum drug level profile was determined. Only minimal differences could be found. One preparation had a significantly higher AUC than one of the others (p less than 0.05), and this difference seemed to be correlated with higher fluctuations of serum levels and, especially, an increased Cmax. Although the group differences are minimal, more important differences could be observed individually. One patient had, with one of the three preparations, a reduction in seizure frequency but simultaneously developed important signs and symptoms of toxicity. It is concluded that all 3 preparations are equally suitable for chronic antiepileptic drug treatment. In a well-controlled patient, however, interchange between preparations is not advisable as their kinetics in individual patients can be sufficiently different to cause toxicity or seizure relapse.
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PMID:Steady state concentrations and diurnal fluctuations of carbamazepine in patients after different slow release formulations. 149 85

The interaction of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) with fenbufen, a nonsteroidal anti-inflammatory agent, in mice was assessed by convulsive seizure and subsequent death in comparison with that of other new quinolones such as DR-3354 (the R-(+)-isomer of ofloxacin), ofloxacin, norfloxacin, enoxacin and ciprofloxacin. Although treatment with each quinolone or fenbufen alone at a dosage level tested in mice showed no changes, coadministration of a large dose of all quinolones and fenbufen caused convulsant death. When compared with the severity of this interaction, it was in the order of enoxacin greater than norfloxacin greater than ciprofloxacin greater than DR-3354 greater than ofloxacin greater than or equal to DR-3355 under these experimental conditions.
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PMID:Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice. 162 42

The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin-induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex.
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PMID:General pharmacology of the new quinolone antibacterial agent levofloxacin. 162 43

The effect of oxiracetam (CGP 21690E, CAS 62613-82-5) on cerebrovascular impairment was investigated in rats. 1. After injection of tranylcypromine (a MAO inhibitor), spontaneously hypertensive rats (SHR) which had been previously infused with norepinephrine (NE) for 14 days displayed stroke-related behaviour including kangaroo-like posture, seizures and death. Administration of oxiracetam at doses of 400 and 800 mg/kg/d p.o. for 14 days before tranylcypromine injection inhibited the stroke-related behaviour. 2. Bilateral common carotid and vertebral artery occlusion induced electroencephalogram (EEG) flattening, the EEG recovering gradually after re-perfusion of cerebral blood flow. Oxiracetam administered after the re-perfusion at a dose of 100 mg/kg, i.v. accelerated the recovery. This facilitatory effect was not seen when either piracetam (50 and 100 mg/kg i.v.) or idebenone (50 and 100 mg/kg i.v.) were administered. 3. Occlusion of middle cerebral artery produced cerebral infarction and disturbed the circadian rhythm of spontaneous motor activity with an relative increase of activity in the light period. Treatment with oxiracetam (400 mg/kg/d p.o.) for 14 days after the occlusion showed a tendency to an improvement in the disturbed circadian rhythm but did not influence the size of brain infarction. From these results, oxiracetam is thought to have a protective effect in cerebrovascular impairment.
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PMID:Effect of oxiracetam on cerebrovascular impairment in rats. 177 53

The bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of 8-(2-phenylethyl)-1-oxa-diazaspiro[4,5]decan-2-one 2-tiophenecarboxylate (decasilate, CAS 76652-72-7) have been evaluated using different experimental models. 1. Decasilate showed a remarkable spasmolytic activity against histamine-induced contractions in the isolated guinea-pig tracheal preparation with an IC50 of 2.7 x 10(-6) mol/l. In addition, the oral administration of decasilate (5-30 mg.kg-1) significantly reduced the histamine aerosol-induced bronchospasm in guinea-pigs. 2. Decasilate had a preventive effect against antigen-induced contractions of ileum segments from sensitized guinea-pigs (EC50 8.0 x 10(-6) mol/l) and relaxed them when added after the antigen challenge (IC50 9.5 x 10(-7) mol/l). 3. Both carrageenin- and dextran-induced rat hind paw oedemas were significantly reduced by the oral administration of decasilate with ED50 values of 169.5 and 34.5 mg.kg-1, respectively. However, it was ineffective against the cotton pellet-induced granuloma in the rat. 4. Furthermore, decasilate had a significant mucolytic activity in rabbits and reduced the number of tussive seizures induced by an aerosol of citric acid in guinea-pigs. The pharmacological profile of decasilate suggests that it might be useful in the management of chronic bronchitis.
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PMID:Evaluation of bronchospasmolytic, antiallergic, anti-inflammatory, mucolytic and antitussive activities of decasilate in experimental models. 189 24

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotension I converting enzyme inhibitor, on the central nervous systems, were studied in experimental animals. Benazepril hydrochloride (3 or 10 mg/kg/d, p.o. for 14 days) dose-dependently inhibited the increase in the blood pressure caused by continuous norepinephrine (NE) infusion in spontaneously hypertensive rats (SHR) and suppressed in seizures induced by a monoamine oxidase inhibitor, tranylcypromine in NE infused SHR. Benazepril hydrochloride transiently increased spontaneous motor activity in mice, tended to inhibit acetic acid-induced writhing in mice and decreased fast wave sleep and slow wave deep sleep on EEG in cats at a high dose of 100 mg/kg p.o. However, benazepril hydrochloride at the same dose showed no effect on other central nervous and sensory systems in experimental animals.
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PMID:General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on central nervous and sensory systems and other functions. 193 Mar 47

The protection by pyroglutamic acid (CAS 98-79-3) and derivatives Ia-i (injected i.p.) against glutamate- and NMDA (N-methyl-D-aspartate) (i.c.v.) induced seizures in mice has been studied in comparison with known antiepileptics and antagonists of excitatory aminoacids. The potency of pyroglutamic acid and some derivatives (Id,f,g,h) against glutamate-induced convulsions was similar to that shown by glutamic acid diethylester and by valproic acid. Interestingly, pyroglutamic acid did not affect NMDA-induced convulsions which were well antagonized by both 2-amino-5-phosphono valeric acid and by diazepam. Thus, pyroglutamic acid may represent the starting for synthesis of excitatory aminoacid antagonists acting at non NMDA receptors.
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PMID:Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice. 198 9

The effects of levocabastine (R 50 547; CAS 79516-68-0) on the central nervous system were studied in comparison with those of diphenhydramine, ketotifen and azelastine. At high doses, levocabastine caused a decrease in locomotor activity, prolongation of thiopental-induced sleep, depression of acetic acid-induced writhing in mice and inhibition of active avoidance response in rats, but these adverse effects were much less potent than those seen in diphenhydramine, ketotifen and azelastine. Oxotremorine-induced tremor and salivation in mice were delayed after extremely high dosage of levocabastine; however, these were much less effective than those seen after diphenhydramine and ketotifen. Levocabastine did not affect the tonic extensor seizure induced by maximal electroshock in mice which is different from that of diphenhydramine. In EEG analysis, levocabastine at a dose of 20 mg/kg caused no significant changes in the EEG recorded from the frontal cortex, occipital cortex, hippocampus and amygdala in rats with chronic electrodes.
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PMID:Central effect of the potent long-acting H1-antihistamine levocabastine. 198 50

Effects of flumazenil (Ro 15-1788, CAS 78755-81-4) on ethanol withdrawal syndrome (EWS) has been investigated in rats. Behavioral EWS symptoms appeared during the first 6 h of ethanol withdrawal. Flumazenil (2.5 and 10 mg/kg i.p.) increased horizontal and vertical locomotor activity significantly and also precipitated abnormal gait and agitation at the beginning of EWS in a dose dependent manner. However, thereafter it reduced the severity of abnormal posture and gait, tail stiffness, agitation and stereotyped behavior in a dose dependent manner. At the 6th hour of EWS, flumazenil (10 mg/kg) reduced total EWS score significantly, but shortened the latency of audiogenic seizures and increased the severity of wet dog shakes. Flumazenil (2.5 and 10 mg/kg) did not elicit behavioral EWS symptoms and audiogenic seizures in non-dependent (control) rats. It did not cause any significant change on locomotor activities in these groups. According to those results, certain actions of flumazenil on the experimental EWS may suggest a potential beneficial effect of this drug in the treatment of EWS in alcoholics, but its enhancing effects on some behavioral EWS symptoms and a potential proconvulsant activity may be a drawback for its use in the treatment of EWS.
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PMID:Effects of flumazenil on ethanol withdrawal syndrome in rats. 771 Apr 30


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