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PubMed2002

Inappropriate pemoline therapy leading to acute liver failure and liver transplantation.

A 36-year-old female, presenting with jaundice, developed acute liver failure requiring orthotopic liver transplantation. On admission, none of the known causative factors for acute hepatitis, including use of drugs, were found to be present. Several days after hospitalization, the patient admitted taking therapy prescribed by a "non-traditional" physician, that she had been using for several years due to overweight and which had recently been modified with the introduction of pemoline. A considerable body of evidence exists in the medical literature showing that pemoline, which is a central nervous system stimulant, has variable hepatotoxic effects, ranging from a mild transient increase of serum transaminases to liver failure, including some lethal cases.

Adult↗
PubMed1966

Magnesium pemoline: enhancement of brain RNA polymerases.

The stimulation by magnesium pemoline of systems that synthesize brain nucleic acid was studied in vivo and in vitro. There are differential effects between true RNA polymerase and pseudo-RNA polymerase. The selective stimulation of true RNA polymerase by magnesium pemoline was not observed with stimulants of the central nervous system and psychotropic agents.

Animals↗
PubMed1967

Activity and responsivity in rats after magnesium pemoline injections.

Rats injected intraperitoneally with magnesium pemoline avoided a buzzing sound (conditioned stimulus) associated with an electric shock to the feet (unconditioned stimulus) more frequently than controls. Drug-injected rats did not avoid the foot shock more frequently than controls, although the experi mental rats did have shorter response latencies fn the active avoidance task. In sub sequent experiments which measured activity changes and response to the buzzing sound alone, it was found that magnesium pemoline caused a lesser decrease in activity level and a more sustained responsivity to the buzzer's. sound than did control injections of tragacanth. This may account for the latency differences observed in the avoidance task.

Animals↗
PubMed1967

Effects of magnesium pemoline and dextroamphetamine on human learning.

Two central nervous system stimulants, magnesium pemoline and dextroamphetamine, were tested to see if they facilitate learning in human subjects. Subjects under placebo learned faster than the subjects under any of the several doses of magnesium pemoline; however, none of these differences reached statistical significance. Subjects who received dextroamphetamine learned significantly more slowly than those who received placebo.

Adult↗
PubMed1967

Pemoline and magnesium hydroxide: lack of effect on RNA and protein synthesis.

Brain RNA polymerase isolated from rats treated with pemoline and magnesium hydroxide (Cylert) was not more active than enzyme from control animals. The drug did not increase enzymic activity in vitro. Pemoline did not significantly affect either RNA or protein synthesis in suspensions of Ehrlich ascites carcinoma cells.

Animals↗
PubMed1984

EEG and clinical findings during pemoline treatment in children and adults with attention deficit disorder. An 8-week open trial.

A clinical study has been conducted on a selected group of 9 children and 12 adults with attention deficit disorder, evaluating the response to the therapy with magnesium pemoline by means of EEG power spectra. Pemoline was given orally in increasing doses ranging from 20 to 80 mg/day. EEG was recorded during baseline and at three fixed intervals during the treatment. Clinical response was assessed by objective and subjective ratings. In the adult sample, the drug produced two opposite patterns of EEG response which allowed us to discriminate by the 1st day of treatment responders who reported a paradoxical calming and non-responders who reported a worsening in anxiety. Inconsistent EEG power changes produced by the drug in children did not allow the discrimination of responders and non-responders. Children did not show paradoxical signs of sedation. EEG and clinical data suggest that adults and children show different drug response and that the paradoxical sedation is present only in adults.

Adolescent↗
PubMed1981

Pemoline-induced Tourette's disorder: a case report.

The author describes the case of a 14-year-old boy who developed Gilles de la Tourette's disorder during pemoline therapy. Unlike other reported cases, the boy's tics did not remit after the pemoline was discontinued.

Adolescent↗
PubMed1986

Pemoline and urinary excretion of catecholamines and indoleamines in children with attention deficit disorder.

To test the hypothesis that any change in urinary noradrenergic excretion accompanies drug-induced improvement in attention deficit disorder with hyperactivity, the authors gave pemoline (mean dose, 2.9 mg/kg of body weight) to 11 boys with this disorder in a 4-week open trial. Pemoline administration improved behavior but did not significantly change urinary catecholamine excretion. Serotonin excretion was unchanged, but phenylethylamine (PEA) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased. Clinical responders and nonresponders did not differ with respect to baseline urinary monoamine excretion or change in PEA and 5-HIAA excretion.

Attention Deficit Disorder with Hyperactivity↗
PubMed1982

Determination of the psychostimulants pemoline, fenozolone and thozalinone in human urine by gas chromatography/mass spectrometry and thin layer chromatography.

Detection of the psychostimulants pemoline (Tradon), fenozolone (Ordinator) and thozalinone (Stimsen) in biological samples (urine) presents certain experimental difficulties. These substances were therefore converted by acid hydrolysis to their common hydrolysis product 5-phenyl-2,4-oxazolidinedione, which can be detected with high sensitivity and selectivity by thin layer chromatography. After silylation with N-methyl-N-trimethylsilyltrifluoroacetamide/trimethylchlorosilane quantitative results can be obtained from the same extract by the proposed GC/MS-method. After a single dose of 30 mg pemoline, levels ranging from one to four mg/l urine were observed.

Central Nervous System Stimulants↗
PubMed1990

Relative efficacy of long-acting stimulants on children with attention deficit-hyperactivity disorder: a comparison of standard methylphenidate, sustained-release methylphenidate, sustained-release dextroamphetamine, and pemoline.

Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind, placebo-controlled, crossover evaluation of the efficacy of standard methylphenidate twice a day and comparable doses every morning of a sustained-release preparation of methylphenidate (SR-20 Ritalin), a sustained-release form of dextroamphetamine (Dexedrine Spansule), and pemoline. The children were participating in a summer treatment program in which they engaged in recreational and classroom activities. Dependent measures include evaluations of social behavior during group recreational activities, classroom performance, and performance on a continuous performance task. Results revealed generally equivalent and beneficial effects of all four medications. Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication. The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion, and the effects lasted for 9 hours. The implications of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed.

Adolescent↗
PubMed1976

[The effect of pemolin on the mitotic activity of Vicia faba L (author's transl)].

The effect of diverse concentrations of 5-phenyl-2-imino-4-oxazolidone (PIO, pemolin, Tradon) on the mitotic activity in lateral roots of Vicia faba L. was studied by aerated and non-aerated hydrocultivation with and without mineral nutrition, respectively. With optimal conditions (aerated nutrient solution) weak PIO-concentrations, most significantly 10(-6) g/ml, effected a marked increase of the mitotic index. Contrarily, strong PIO-concentrations (10(-4) and 3 X 10(-4) g/ml = saturated solution) significantly decreased the mitotic index though simultaneously preserving the mitotic activity in long-term experiments, when on account of nutrient deficiency it had already collapsed in weak PIO-concentrations and the controls. The activating effect of weak PIO-concentrations compared with the controls is more significant in stress situations (nutrient deficiency, O2-deficiency) than under optimal conditions. Furthermore a slight acceleration of mid-mitotic phases (metaphase--anaphase) recognized by a marked decrease in percentage of these phases, can be stated with weak PIO-concentrations, again particularly so with 10(-6) g/ml. In total, dependent on concentration, pemolin presumably may either activate or suppress cell metabolism and particularly the mitotic cycle. The exact site of action of the substance is still unknown.

Air↗
PubMed1990

Pemoline-associated hepatic injury.

Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic.

Adolescent↗
PubMed2000

A verification of psychostimulant-induced improvement in sustained attention in rats: effects of d-amphetamine, nicotine, and pemoline.

Previous studies from this laboratory have demonstrated that a variety of psychostimulant drugs can improve the performance of rats trained in a 2-choice stimulus detection task in which the correct responses are indicated by a briefly illuminated light. To enhance the construct validity of the task for assessing sustained attention, the procedure was modified so that the precue interval across trials varied unpredictably between 3, 7, and 11 s. After training rats (N = 17) so that their baseline accuracy levels stabilized between 75% and 88% correct, their performance was assessed after administration of d-amphetamine (0.125-0.75 mg/kg sc), nicotine (0.25-0.75 mg/kg sc), and pemoline (5.0-30.0 po). At certain doses all 3 drugs induced performance improvements in mean choice accuracy and choice response time. Because the precue intervals varied unpredictably and the cue durations used to maintain the rats' baseline accuracy levels were typically short (range = 70-500 ms), the task conforms to most conditions typically required for assessing sustained attention. Results verify the proposal that psychostimulant drugs can enhance the attentiveness of animals in a fashion similar to that documented in humans.

Animals↗
PubMed1976

Clinical trial with amantadine and pemoline in elderly patients.

In a controlled clinical trial, amantadine 400 mg daily, 200 mg daily and 200 mg daily given with 20 mg of pemoline daily were compared with placebo in the treatment of elderly patients suffering from involutional cerebropathy characterized by psychomotor slowing down. The results showed that amantadine 400 mg daily was superior to placebo but was associated with a high incidence of side-effects (37 per cent), amantadine 200 mg daily was not superior to placebo but when pemolint 20 mg daily was added the combination was superior to placebo and few side-effects were reported.

Aged↗
PubMed2000

Severe hypotension in a patient receiving pemoline during general anesthesia.

IMPLICATIONS: This case reports hypotension under general anesthesia in a patient taking pemoline. Vigilance for unexpected hypotension is important in patients who are treated with psychostimulants. If hypotension occurs, vasopressors that act directly on adrenergic receptors should be used.

Anesthesia, General↗
PubMed1979

Pharmacokinetics of pemoline in plasma, saliva and urine following oral administration.

1 Pemoline concentrations were measured in plasma and saliva following a single oral dose (37.5 or 50.0 mg) to healthy volunteers. In addition urinary excretion rates and cumulative urinary excretion of the parent compound and its oxazolidinedione metabolite were determined. 2 The plasma curves exhibited a mean elimination half-live of 11.0 +/- 1.2 h (n=4). Peak levels were reached at 2.7 +/- 0.6 h (n=4). The saliva concentrations were about 50% lower than the corresponding plasma concentrations during the elimination phase. During the absorption phase irregularities in the saliva to plasma concentration ratios were observed. 3 In urine 47.0 +/- 8.4% of the dose (n=6) administered was excreted as unchanged drug and only 3.7 +/- 0.8% (n=3) as the oxazolidinedione metabolite. Urinary half-lives were slightly shorter than the corresponding plasma half-lives.

Administration, Oral↗