Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1988, the specific benzodiazepine antagonist, flumazenil (Anexate Roche), was introduced in clinical practice in Czechoslovakia for analgesia. A pilot study was initiated to establish whether .1 mg of flumazenil iv was capable of accelerating the psychic recovery of women after abortion. 30 healthy women aged 17-25 received a combination of .1 mg/kg-1 diazepam iv together with .88 mg/kg-1 ketamine iv. Another group of 10 women of the same age range were given .05 mg/kg-1 of midazolam iv. Flumazenil, in a dose of .1 mg iv, was administered to the women following the completion of the procedure, i.e., about 5-7 minutes after giving benzodiazepine. The effect of flumazenil became apparent 30 seconds after iv administration. The hypnotic-sedative effect of benzodiazepine set in after 30-60 seconds, and its biological half-life was 50-60 minutes. After administration of midazolam, an especially strong sedative effect was produced for operative intervention. The psychic effects of ketamine lasted only a little while and no occurrence of psychomimetic symptoms were observed as determined by an orientation test of place, time, and space. Retrograde amnesia was complete during the procedure. Partial amnesia occurred after administration of flumazenil. The lowest flumazenil doses antagonized only the hypnotic and sedative effects of benzodiazepine but did not influence the anxiolytic and amnestic effects. Systolic pressure increased by 10 torr: the pulse rate increased on the average from 74.4 - 84.8 beats/minute. Mild ataxia occurred in women who attempted to get out of bed, but 60 minutes after completion of the procedure, the patients were able to walk without ataxia. It was clearly demonstrated that the sedative-hypnotic effects of benzodiazepine can be subdued after abortion, shortening the period required for the recovery of the patient.
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PMID:[Initial experience with flumazenil (Anexate Roche) for abortion]. 250 17

1. GYKI 52466 is a benzodiazepine derivative that has muscle relaxant and anticonvulsant properties thought to be mediated by highly selective, noncompetitive antagonism of non-NMDA receptors. However, recent electrophysiological data showed that, in addition to non-NMDA receptors, the GABAA-receptor associated benzodiazepine site is involved in the depressant effect of GYKI 52466 on spinal reflex transmission. In view of the structural similarities between the 2,3 benzodiazepine derivative GYKI 52466 and 1,4-benzodiazepines such as diazepam, the benzodiazepine site of GABAA receptor complex could also be involved in the anticonvulsant activity of GYKI 52466, which has not yet been proven. This prompted us to study the effect of the benzodiazepine receptor antagonist, flumazenil, on anticonvulsant and adverse effects of GYKI 52466 in different seizure models in mice. The non-NMDA antagonist, NBQX and diazepam were used for comparison. 2. Seizure threshold models for different types of generalized seizures were used. The threshold for maximal (tonic) electroshock seizures (MES) was significantly increased by GYKI 52466 (10-20 mg kg-1), NBQX (80-120 mg kg-1) and diazepam (5 mg kg-1) shortly after i.p. drug administration. The same dose-range of the non-NMDA antagonists also significantly increased the threshold for myoclonic and clonic seizures induced by i.v. infusion of pentylenetetrazol (PTZ), although the magnitude of threshold increases obtained with the respective drugs, differed, at least in part, from that seen in the MES experiments. GYKI 52466 was clearly less potent in increasing PTZ thresholds for myoclonic and clonic seizures than on the MES threshold, while NBQX exerted about the same potency in both models. In contrast to the non-NMDA antagonists, diazepam was capable of increasing themyoclonic and clonic PTZ seizure threshold at much lower doses than the MES threshold. The PTZ threshold for tonic seizures was markedly increased by GYKI 52466, while NBQX and diazepam were clearly less potent in this respect.3. With respect to adverse effects, GYKI 52466 and NBQX induced significant seizure threshold increases in the different seizure models only at doses which caused sedation and ataxia, while diazepam increased the myoclonic and clonic PTZ seizure threshold at doses below those inducing motor impairment.4. Flumazenil (5-20 mg kg-1) antagonized the anticonvulsant and adverse effects of diazepam but not GYKI 52466. Instead, the anticonvulsant effect of GYKI 52466 was potentiated by flumazenil in some experiments. The anticonvulsant activity of NBQX was slightly reduced by flumazenil in the MES model but not in the PTZ test.5. The data indicate that the GABAA receptor-associated benzodiazepine site is not critically involved in anticonvulsant or adverse effects of GYKI 52466. However, both GYKI 52466 and NBQX were unable to increase seizure thresholds at doses below those inducing sedation and motor impairment,thus demonstrating that non-NMDA antagonists lack a selective anticonvulsant action in standard models of generalized seizures.
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PMID:Effects of the non-NMDA antagonists NBQX and the 2,3-benzodiazepine GYKI 52466 on different seizure types in mice: comparison with diazepam and interactions with flumazenil. 788 91

The ability of the GABA(A)-receptor-subtype-selective hypnotic zaleplon to produce physical dependence was compared to the nonselective benzodiazepine triazolam. Progressively increasing doses of zaleplon and triazolam were given to baboons by intragastric infusion once each day, with doses increasing every 17 days. Next, the highest dose was given for 10-34 additional days by continuous infusion. Both drugs produced increases in food-maintained lever pressing, ataxia, and time to complete a fine motor task. Plasma levels increased dose-dependently; drug was detectable 24 h after higher doses. Flumazenil produced a mild or intermediate precipitated-withdrawal syndrome on day 14 of all dosing conditions. When drug delivery ended after 85-100 days, a benzodiazepine-type withdrawal syndrome occurred. Physical dependence potential of zaleplon and triazolam appear similar.
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PMID:Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons. 1106 85

The behavioral effects of abecarnil, a beta-carboline which has been suggested to function as a partial and/or selective agonist at the benzodiazepine receptor, were assessed in baboons. In a chronic administration study, 100mg/kg/day abecarnil for 6-8 weeks produced few signs of sedation: lip droop and intention tremor were observed in two of the four baboons. Flumazenil administration (5mg/kg, i.m.) on day 8 of chronic abecarnil produced only a mild precipitated benzodiazepine withdrawal syndrome. Vehicle substitution after 6-8 weeks of chronic abecarnil produced transient signs of a mild withdrawal syndrome, including decreased food intake, but did not produce vomiting, twitches/jerks or seizures. In a self-injection study, abecarnil (0.032-1.0mg/kg/injection) did not maintain rates of self-injection above vehicle control levels; higher rates of self-injection were maintained in the same animals by cocaine (0.32mg/kg/injection) and triazolam (0.01mg/kg/injection). The highest i.v. abecarnil dose (1.0mg/kg/injection) produced sedation and ataxia in two of the three baboons. In a drug discrimination study, generalization from lorazepam training conditions (1.8mg/kg, p.o.) to abecarnil was an increasing function of dose, and maximal drug lever responding occurred reliably in all baboons 5h after 10-32mg/kg, p.o. abecarnil administration. Flumazenil (0.32mg/kg, i.m.), given 4h after abecarnil, completely antagonized the abecarnil stimulus in test sessions 1h later. The present experiments show that the behavioral profile of abecarnil is clearly distinguisable from that of benzodiazepines.
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PMID:Behavioral pharmacology of abecarnil in baboons: self-injection, drug discrimination and physical dependence. 1122 53

Consumption of Anaphe larva had been reported to cause seasonal ataxia and impaired consciousness. Therefore this study examined the neuropharmacological and mechanism(s) of action of aqueous extract of Anaphe venata in rats. Behavioural effects namely rearing, stretching, sniffing and ataxia were determined after the intraperitoneal administration of aqueous extract of Anaphe larva in rats. Animals were divided into groups and graded doses (100, 200 and 400 mg/kg, i.p.) of extract were administered. The control group was administered normal saline (vehicle). The effects of scopolamine (3 mg/kg, i.p.), flumazenil (2 mg/kg, i.p.), naloxone (2.5 mg/kg, i.p.), and thiamine (1 mg/kg, i.p.) on the observed behavioral changes were also examined. The effects of the extract administered intraperitoneally at a dose of 200 mg/kg on the amphetamine-induced stereotypy and locomotion were evaluated. Aqueous anaphe extract induced significant (p< 0.01) stretching and ataxia behavioural effects while it inhibited rearing behaviour when compared with the vehicle-treated group. However, it had no significant effect on sniffing behaviour. Scopolamine reversed all the effects of the extract on rearing, stretching and ataxia. Both Flumazenil and naloxone only reversed the effects of the extract on stretching and ataxia-induced behaviours significantly. However, thiamine potentiated both stretching and ataxia-induced behaviours. The extract inhibited the amphetamine-induced stereotype behaviour and locomotion. In conclusion, these results showed that these anaphe-induced behavioural effects are mediated via cholinergic, GABAergic, opioidergic and dopaminergic receptor systems with strong muscarinic-cholinergic receptors involvement in ataxia-induced behaviour. We therefore suggest that muscranic-cholinergic like drugs may be of benefit in the management of patients that present with clinical condition of seasonal ataxia.
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PMID:Neuropharmacological profile of aqueous extract of Anaphe venata larva (Notondotidae) in rats. 2246 4

Two dogs presented to the emergency service after accidental ingestion of afloqualone tablets, a muscle relaxant used for back pain in humans. Toxic effects of the drug in these dogs included vomiting, respiratory depression, seizures, ataxia, bradycardia, and hematuria. Treatment consisted of fluid diuresis, furosemide, and propofol. Flumazenil, a gamma-amino butyric acid antagonist, was administered intravenously; however, it was not effective in stopping the seizures in these dogs. Both dogs recovered with supportive treatment. To the authors' knowledge, this is the first documented report of afloqualone intoxication in dogs.
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PMID:Accidental afloqualone intoxication in two dogs. 2914 47