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)

The interactions of caffeine (10 mg/kg p. o.) with various doses of ethanol, diazepam or pentobarbital were investigated by observing the ambulatory activity of mice. The ambulatory activities after the coadministration of caffeine with ethanol (1.6, 2.4 and 3.2 g/kg p. o.) were significantly higher than those after the single administration of the corresponding doses of individual drugs. Ethanol alone significantly increased the activity with ataxia at 2.4 and 3.2 g/kg, suggesting that 1.6 g/kg of ethanol was an optimum dose for studying the interaction of caffeine with ethanol. Although diazepam (0.25, 0.5 and 2 mg/kg s. c.) and pentobarbital (1, 3 and 10 mg/kg s. c.) alone did not change the activity, they significantly reduced the effect of caffeine. Naloxone (1 and 5 mg/kg s. c.) did not modify the effect of caffeine alone, but, at 5 mg/kg, it was effective in significantly reducing the ambulation-increasing effect of caffeine with ethanol (1.6 g/kg) to nearly the level of caffeine alone. Ca-cyanamide (5 mg/kg p. o., pretreatment 30 min before), reserpine (1 mg/kg s. c., pretreatment 4 hr before) and alpha-methyl-p-tyrosine (200 mg/kg i. p., pretreatment 1 hr before) reduced the ambulation increment induced by caffeine alone or combination of caffeine with ethanol. Ethanol, diazepam and pentobarbital are classified as CNS depressants, and caffeine as a CNS stimulant. However, the present experiment demonstrated that the interaction of caffeine with ethanol was very different from that of caffeine with diazepam or pentobarbital. In the enhancing interaction of caffeine and ethanol, both dopaminergic and endogenous opioid systems may be involved.
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PMID:Ethanol enhances, but diazepam and pentobarbital reduce the ambulation-increasing effect of caffeine in mice. 144 12

The intracerebrally administered dynorphin-B produced not only an antinociceptive response but a motor dysfunction such as "barrel-rolling", circling, jumping or ataxia in mice. These two effects were observed in a same dose range. Both responses were also produced by a nonopioid fragment, des-Tyr-dynorphin-B. Bestatin, an aminopeptidase inhibitor, markedly potentiated the antinociceptive response induced by dynorphin-B but not the motor dysfunction. Bestatin did not affect the responses produced by des-Tyr-dynorphin-B. In the presence of bestatin, low doses of dynorphin-B produced an antinociceptive response without the motor dysfunction. Naloxone antagonized the potentiated antinocicpetion but had no effect on the motor dysfunction. These results suggest that dynorphin-B produced an analgesia through opioid receptors and that this peptide also induced a motor dysfunction through a nonopioid receptor.
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PMID:Bestatin potentiates the antinociception but not the motor dysfunction induced by intracerebrally administered dynorphin-B in mice. 256

In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.
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PMID:Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol. 294 27

Opioid agonists were used to investigate the modulation of seizures mediated by mu, kappa and delta opiate receptors in the seizure-sensitive Mongolian gerbil. Morphine (1.0-25 mg/kg, s.c.) were used as prototypic agonists for mu, kappa and delta opiate receptors. Each opioid decreased the incidence and severity of the seizure as compared to control values. The anticonvulsant effects of morphine (10 mg/kg, s.c.) and ketocyclazocine (0.5 mg/kg, s.c.) were reversed by naloxone (1.0 mg/kg, s.c.), while the anticonvulsant effects of N-allylnormetazocine (2 mg/kg, s.c.) were not significantly changed by naloxone. Additionally, abnormal behavior was observed following administration of the opioids. Morphine (10 mg/kg, s.c.) produced excitation and hyperresponsiveness with intermittent cataleptic-like states. Ketocyclazocine (10 mg/kg, s.c.) predominantly produced a stuporous, immobile state, accompanied by some loss of posture. N-allylnormetazocine (10 mg/kg, s.c.) produced ataxia and stereotypic side-to-side head nodding . Naloxone was able to reverse the behavioral effects produced by morphine and ketocyclazocine but not those produced by N-allylnormetazocine. The data presented are consistent with earlier studies which demonstrated the anticonvulsant effects of beta-endorphin in the gerbil. This study further suggests that opioids have a protective role against seizure activity in the gerbil and the opioid anticonvulsant effect is not specific to one type of opioid agonist.
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PMID:Similar anticonvulsant, but unique, behavioural effects of opioid agonists in the seizure-sensitive Mongolian gerbil. 633 Jun 6

The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 micrograms/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 micrograms/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 micrograms/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.
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PMID:Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat. 681

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Common signs of toxicity of these drugs are central nervous system manifestations such as altered sensorium, lethargy, ataxia, and nystagmus. Some ingestions can paradoxically precipitate seizures and even status epilepticus. Sodium valproate can cause hyperammonemic encephalopathy and cerebral edema. Carbamazepine is implicated in cardiac arrhythmias and hyponatremia. Phenobarbital causes sedation, respiratory depression, and hypotension. In suspected overdose, apart from the routine laboratory tests, serum levels of the drug should be sent. Serial levels should be measured, as drug toxicity can be prolonged. Treatment of all these overdoses begins with stabilization of airway, breathing, and circulation, and endotracheal intubation being performed to protect the airway in patients with altered mental status. For decontamination, a single dose of activated charcoal should be given. Multidose of activated charcoal may be useful in phenytoin, carbamazepine, and phenobarbital overdose. Naloxone and carnitine are indicated in valproate overdose. Carbamazepine overdose can cause a widened QRS complex and arrhythmias, which can be treated with sodium bicarbonate. Forced alkaline diuresis is no longer advocated for phenobarbital poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup have formulated guidelines for extracorporeal removal of all these drugs. In most cases, hemodialysis is preferred. Other modalities include charcoal hemoperfusion (especially for carbamazepine) or continuous venovenous hemodialysis. Patients who ingest long-acting preparations should be monitored for longer periods.
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PMID:Antiepileptic Overdose. 3202 Oct 7