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)

Cats were treated once daily for 35 days with flurazepam (FZP). Different groups received 2, 5 or 20 mg/kg per day. A fourth group was started at 20 mg/kg per day, then the dose was increased to 30, and finally 40 mg/kg per day. Muscle relaxation, ataxia, and other measures of neurological impairment were used to measure drug actions. Tolerance developed rapidly, and no FZP effects were seen after 2-3 weeks of treatment with 2 or 5 mg/kg. Doses of 2-100 mg/kg FZP were injected i.p., 48 h after the last dose of chronic treatment with 2 or 5 mg/kg, and peak FZP effects were recorded. There was an approximate 10-fold shift to the right of the dose-response curve, indicating a large degree of functional tolerance after 5 weeks of FZP treatment. The pattern of tolerance, as measured by dose-response analysis, suggests that it may be different from the functional tolerance developed during barbiturate administration.
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PMID:Nature of functional tolerance produced by chronic flurazepam treatment in the cat. 711 80

SDZ EAA 494 (D-CPPene) was characterized as a competitive NMDA antagonist, having a pA2 value against NMDA depolarizations in frog spinal cord and rat neocortex of 6.7-6.8 and a pKi of 7.5 in a [3H]CGP39653 binding assay, with no action on other receptors or amine reuptake. The compound was orally active in rodent maximal electroshock models with an ED50 of around 16 mg/kg, was protective in rats even 24 hours after oral application and had an oral therapeutic index of around 8. Muscle relaxation, ataxia, flattened body posture and reduced acquisition of a passive avoidance task, suggesting potential effects on memory formation, occurred at supra-anticonvulsant doses in rodents, with PCP-like stimulatory effects produced only by high i.p. doses or constant i.v. infusions. This favourable profile is discussed in relation to the negative outcome of a recent trial of the compound in patients with intractable epilepsy. The conclusion is drawn that standard models for screening new anticonvulsants are inappropriate to seeking drugs active in patients with a protracted convulsive history. The anti-ischaemic action of SDZ EAA 494 encourages further testing in brain trauma, in which the anticonvulsant action of the compound may be an added benefit.
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PMID:The pharmacology of SDZ EAA 494, a competitive NMDA antagonist. 789 35

Ten common marmosets (Callithrix jacchus) and 10 black-tufted marmosets (Callithrix penicillata) were immobilized to compare the anesthetic effects of racemic ketamine and (S+) ketamine in combination with midazolam. The animals were distributed into four groups: five common marmosets (group CJR) and five black-tufted marmosets (group CPR) received 9.8 +/- 1.4 mg/kg of racemic ketamine, and five common marmosets (group CJS) and five black-tufted marmosets (group CPS) received 10.4 +/- 1.6 mg/kg of (S+) ketamine. All groups received similar dosages of midazolam (1.0 +/- 0.15 mg/kg). During immobilization, heart rates, respiratory rates, rectal temperatures, and muscle relaxation scores were recorded at 5, 10, and 20 min after initial injection. Quality of induction and quality of recovery were evaluated in each marmoset by recording physical reactions including withdrawal reflexes, involuntary movements, salivation, compulsive licking, catalepsy, and ataxia. There were no significant differences in the induction, immobilization, and recovery times between the four groups. Similarly, there were no significant differences between groups in heart rates, respiratory rates, or body temperatures, although there was a significant decrease in respiratory rates over time in group CPR. In addition, the CJR and CPS groups showed significant decreases over time in rectal temperature. Muscle relaxation was more profound in the CPR group than in the other groups. Compulsive licking, involuntary movements, salivation, and withdrawal reflexes were observed more frequently in animals given S(+) ketamine; but in general, racemic ketamine and S(+) ketamine had similar effects in all callitrichines. Further studies are required to confirm that S(+) ketamine has different potency in these species.
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PMID:Comparison of racemic ketamine versus (S+) ketamine when combined with midazolam for anesthesia of Callithrix jacchus and Callithrix penicillata. 2094 34