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Interaction between ethanol and dextroamphetamine: effects on psychomotor performance.

The objective of this study was to investigate the interaction between ethanol and dextroamphetamine with regard to psychomotor performance. Twelve healthy, male, paid volunteers, moderate users of ethanol and amphetamines, participated in this study. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Five minutes before the termination of ethanol or placebo ingestion, dextroamphetamine elixir (0.09 mg/kg, 0.18 mg/kg or placebo) diluted in 50 ml of orange juice was administered. Subjects were tested in a single-blind, latin-square, crossover design with each of the following six conditions: placebo ethanol/placebo dextroamphetamine; placebo ethanol/low-dose dextroamphetamine; placebo ethanol/high-dose dextroamphetamine; ethanol/placebo dextroamphetamine; ethanol/low-dose dextroamphetamine; and ethanol/high-dose dextroamphetamine. The variables measured in this study were: subjective rating of ethanol and dextroamphetamine intoxication, accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI task), blood ethanol concentration by breath analyzer, and plasma concentrations of dextroamphetamine by gas chromatography. Results indicate ethanol induced decrements in performance of the skills necessary to drive an automobile were significantly decreased by dextroamphetamine in a dose-response fashion. The administration of dextroamphetamine did not decrease the subjective ratings of ethanol intoxication.

Adult

Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis.

Double-blind crossover comparison of methylphenidate hydrochloride, dextroamphetamine sulfate, and caffeine after placebo washout in 29 children with minimal brain dysfunction (MBD) showed on six ratings that methylphenidate and dextroamphetamine were significantly (P less than .05 to P less than .001) better than placebo and caffeine, but not significantly (P less than .05) different from each other. Placebo, caffeine, and ratings before drug did not differ significantly. Of 26 drug responders, 12 responded best to dextroamphetamine, ten to methylphenidate, and one to caffeine. The latter child showed no improvement at all with either prescription stimulant. Methylphenidate and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant. All three drugs showed significant (P less than .05) weight loss and cardiovascular side effects, the latter possibly spurious. Dextroamphetamine showed a significant (P less than .05) decrease from placebo in "tummyaches."

Attention Deficit Disorder with Hyperactivity

Emotional symptomatology in obese patients treated with fenfluramine and dextroamphetamine.

Emotional sympomatology data on 78 obese females treated for 3 weeks with fenfluramine, dextroamphetamine, or placebo were evaluated. These obese females were shown to be considerably less emotionally disturbed than neurotic females, and similar in emotional symptomatology to other females seeing physicians for nonpsychiatric complaints. Even within these marginally sympatomatic patients, fenfluramine and dextroamphetamine were significantly more effective than placebo in reducing anxious, depressive, and anxious-depressive symptomatology. Fenfluramine was particularly effective in alleviating anxiety in patients who were initially higher in anxiety. Most important, fenfluramine produced significantly greater weight loss than dextroamphetamine in patients with higher levels of anxiety and depression, while dextroamphetamine was an especially effective anorexic in low anxious patients. Differences in initial anxiety and depression, even within relatively normal patients, may well affect results obtained with fenfluramine and dextroamphetamine in the short-term treatment of obesity.

Adult

Dextroamphetamine with morphine for the treatment of postoperative pain.

In a double-blind, single-dose study, dextroamphetamine combined with morphine was compared with morphine alone to determine the relative efficacy of the combination given intramuscularly for postoperative pain. Each of 450 patients received one treatment of morphine sulfate (3, 6 or 12 mg) with dextroamphetamine (0, 5 or 10 mg). Analgesia, as measured by the patients' subjective responses to questions about relief of pain, was augmented when dextroamphetamine was given with morphine; the combination of dextroamphetamine, 10 mg, with morphine was twice as potent as morphine alone, and the combination with 5 mg was 1 1/2 times as potent as morphine. In simple performance tests, and in measures of side effects, dextroamphetamine generally offset undesirable effects of morphine (sedation and loss of alertness) while increasing analgesia. Effects on blood pressure, pulse and respiratory rate were minimal.

Adult

The effect of the stimulant drugs, dextroamphetamine and methylphenidate, on secretion of growth hormone in hyperactive children.

The stimulant effect of L-dopa (125 to 500 mg) was compared to dextroamphetamine and methylphenidate, 15, and 20 mg, respectively, on growth hormone secretion in 20 hyperactive children. All three stimulants were responsible for peak GH concentration in serum at 60 minutes after drug ingestion; there was no significant difference between the mean GH level at any time of sampling. Seven of the children were retested with L-dopa and dextroamphetamine after six to eight months of treatment with methylphenidate. After treatment, there was a tendency to higher zero time levels of GH, and to delayed and/or paradoxical response to dextroamphetamine. The findings indicate an acute and a probably long-term effect of dextroamphetamine and methylphenidate on the homeostasis of growth hormone. The possible long-term adverse effects of these drugs on the growth of children indicates the need for caution to the widespread use of these agents.

Adolescent

Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Replication, time response, and differential effect by diagnostic group and family rating.

Double-blind crossover randomized Latin square comparison of placebo, dextroamphetamine, and levoamphetamine in 31 consecutively diagnosed children with minimal brain dysfunction (MBD) replicated a smaller nonrandom study. Both isomers showed significantly more benefit than placebo but were not significantly different from each other. Dextroamphetamine showed a nonsignificant trend of superiority over levoamphetamine. Of 25 subjects who responded well to drugs, three responded only to levoamphetamine, five only to dextroamphetamine, and 17 to both. This study seems to confirm the efficacy of levoamphetamine in MBD. An unsocialized aggressive subgroup (308.4) showed a nonsignificant trend for levoamphetamine superiority, in contrast to the hyperkinetic (308.0) and overanxious (308.2) subgroups. Those who responded best to levoamphetamine tended (not significantly) to be from poorer functioning families. Parents' ratings, but not teachers' or psychiatrists' ratings, showed significant placebo effect.

Amphetamine

Methylphenidate, dextroamphetamine, and levamfetamine. Effects on schizophrenic symptoms.

Methylphenidate hydrochloride dextroamphetamine sulfate, and levamfetamine succinate have potential as pharmacologic tools for the indirect evaluation of the role of neurotransmitters in schizophrenia. In actively ill schizophrenic patients, methylphenidate administered intravenously causes a brief but clear intensification of preexisting psychotic symptoms, such as hallucinations and delusions. In our study, methylphenidate, dextroamphetamine, and levamfetamine were administered in equimolar doses to schizophrenic patients. Methylphenidate was a more effective activator of symptoms than dextroamphetamine, which in turn was more effective than levamfetamine. Levodopa (L-dopa) given orally also reportedly produces a temporary worsening of schizophrenic symptoms. While these findings augment a body of information suggesting that dopamine and norepinephrine may play a role in the activation of schizophrenic symptoms, our findings with methylphenidate (reportedly weak in eliciting stereotyped behaviour in rat) and our review of the literature indicate complexities that remain to be resolved. There is some utility of the procedure for differential diagnosis and selective therapy, but this is still of occasional and limited potential.

Acute Disease

The effects of LSD-25 and dextroamphetamine on the use of defensive language.

Verified that psychotomimetics attenuate verbal defense mechanisms. This was accomplished by reanalyzing the 5-minute monologues of 7 neurotic depressives who participated in a project (Mechaneck, Feldstein, Dahlberg, & Jaffe, 1968) that examined the effects of LSD and dextroamphetamine on timing aspects of speech. Dosages were subhallucinatory: 15-25 mg dextroamphetamine, 50-100 mg LSD, and a matching placebo. Volunteers received each drug (double-blind) seven or eight times on a random schedule over a 1 1/2-year period; there was a 3-week intertrial interval. The patient provided 5-minute monologues both before and after drug effects. The monologues were transcribed and scored for formal measures of defensive language. Results indicated that LSD caused individuals to make more personal statements and to use explanation and evaluations less often. Dextroamphetamine was found to decrease the use of nonpersonal references.

Adult

Comparative effects of dextroamphetamine and reserpine on halothane and cyclopropane anesthetic requirements.

Cyclopropane minimum alveolar concentration (MAC) values in dogs following intravenous administration of 0.5, 1 or 2 mg/kg of dextroamphetamine were 27.8, 28.4, and 28.4 volumes percent, respectively. Those values did not differ significantly from each other but were 44 percent greater than average control (no dextroamphetamine(MAC values. Halothane MAC values following the same dextroamphetamine doses were 1.51, 1.71, and 1.64 volumes percent. These values were 75 percent greater than average controls, and this increase was significantly more than the 44 percent noted with cyclopropane. In contrast, 2 mg/kg of reserpine decreased halothane MAC 20 percent vut decreased cyclopropane MAC 40 percent- the difference between the two anesthetics again being statistically significant. These results suggest that alteration of anesthetic potency by centrally active adrenergic drugs depends on the sympathetic activity induced by the anesthetic. Conversely, this suggests that anesthetics may influence their own potency by altering central nervous system adrenergic activity.

Animals

Effects of dextroamphetamine on psychomotor skills.

Twelve healthy male volunteers were given 0, 5, 10, 15 mg/70 kg dextroamphetamine orally in a randomized double-blind fashion. Blood pressure increased linearly with dose while heart rate was unchanged. Although selected individual tests of stance stability and motor function improved in a dose-related fashion, a generalized improvement in performance was not found. Delayed Auditory Feedback (DAF) failed to show improvement in mental performance after dextroamphetamine.

Acoustic Stimulation

Dextroamphetamine and placebo practice effects on selective attention in hyperactive children.

Three groups of boys referred to a hospital study unit for evaluation of hyperactive behavior were tested on a classification task involving selective attention while on either dextroamphetamine (D) or placebo (P). In two sessions, groups had D first, P second (DP), or PD, or PP. Amphetamine reduces a response times in general and reduces interference due to orthogonally varying irrelevant information. Practice while on placebo improves performance in a subsequent placebo session. Practice while on amphetamine does not, however, improve performance in the subsequent session on placebo. Assessment of the extent of the drug-state-related practice effect is necessary for evaluation of long-term benefits of dextroamphetamine therapy in these children.

Attention

Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia.

OBJECTIVE: The authors sought to determine if an acute dose of dextroamphetamine might have positive effects on affect and cognition in schizophrenic patients maintained on a regimen of haloperidol and, if so, what variables might predict such improvements. METHOD: Twenty-one patients with chronic schizophrenia who were hospitalized on a research ward received a single oral dose of dextroamphetamine (0.25 mg/kg) in a double-blind, placebo-controlled, crossover study. All patients were receiving 0.4 mg/kg per day of haloperidol. Cognitive tests, motor tests, global ratings, mood ratings, and videotape ratings were used to determine the effect of the coadministration of these drugs. Ventricle-brain ratios derived from CT scans were used to predict response to the coadministration of these drugs. RESULTS: Amphetamine improved performance on a measure of concept formation on the Wisconsin Card Sorting Test but did not result in changes in performance on tests of memory or attention. As a group, the patients were more active and performed psychomotor tests more quickly while receiving amphetamine. Six patients were judged by clinical raters to have improved in terms of affect, cooperation, and engagement with the environment. Improvement was associated with enlarged cerebral ventricles and increases in blink rate from the placebo to the active drug condition. No patient unequivocally worsened. CONCLUSIONS: These results may be consistent with the theory that coadministration of amphetamine and haloperidol produces relatively selective enhancement of cortical dopaminergic activity. However, because of the acute nature of the trial and the specialized research environment in which it was conducted, the authors do not advocate amphetamine as a routine clinical treatment of schizophrenia.

Adult

A comparative study of the driving effects of dextroamphetamine and yogic meditation on muscle control for the performance of balance on balance board.

The work is aimed to compare the relative strength of dextroamphetamine and yogic meditation on the performance of 3 different groups of medical students to concentrate on the task to balance on a balance board. Group A subjects were mediators, group B subjects were given orally 5 and 10 mg of dextroamphetamine in a capsule, 1 hr prior to the test. Group C subjects were given same capsule but with lactose in place of the drug (placebo). This last groups served as control for the study. The balance index calculated taking into account their balance time and error score at each trial of 5 min duration showed that the performance of the group B (drug) had declined with overall percentile fall of 40.6% as compared to the performance of the controls (placebo) whereas, the performance of Group A (meditators) went on steadily and progressively increasing throughout the period of 10 trial days with overall percentile rise of 27.8%. The results were conclusive to confirm earlier reports that amphetamine is not of use for improvement of task rather, it deteriorates the task performance. Contrary to that, yogic meditation is of merit to achieve concentration for mental as well as physical task.

Adolescent

Mutagenicity obtained experimentally by oral administration of dextroamphetamine sulphate to the rat.

Research work on the possible mutagenic effects of the amphetamine, sympathomimetic amine, was carried out on the rat. The method used was the dominant lethal assay, in its sub-acute form. Dextroamphetamine sulphate was administered orally. At the dosage and frequency of the test, dextroamphetamine sulphate was found to be a significantly mutogenic agent. The over-all mutagenic index was 13.92% (P less than 0.01) for the test group and 8.90% for the control group.

Abnormalities, Drug-Induced

Subjective responses and excretion patterns of dextroamphetamine after the administration of therapeutic doses.

Twelve male medical and graduate students received dextroamphetamine sulfate in doses of 0, 5, 10, and 15 mg/70 kg body weight. The study was conducted in a double-blind manner, and treatments were assigned according to randomized, complete block design. The drug was given orally and subjects were instructed not to eat 3 1/2 h prior to administration. After administration, total urine output was collected for 12 h; no attempt was made to control urinary pH to more realistically approach the general clinical usage of amphetamines. The urine was pooled into two 6-h segments and analyzed for amphetamine concentration. Subjective impressions of the treatments were also evaluated by means of the Cornell Medical Index Questionnaire. Results showed that approximately 30% of the total dose was excreted unchanged within 12 h after administration. The amount excreted agreed very closely with the doses given and paralleled the scores for subjective impressions by the subjects. None of the subjects felt that their driving would be impaired for any of the doses administered. This study indicates that under ordinary conditions (in which pH is not artificially controlled), therapeutic doses of dextroamphetamine can be detected in urine for up to 12 h after oral administration.

Administration, Oral

Growth of hyperkinetic children taking methylphenidate, dextroamphetamine, or imipramine/desipramine.

One hundred children with the hyperkinetic syndrome or minimal brain dysfunction syndrome were treated with medication: 60 with methylphenidate (Ritalin), 24 with dextroamphetamine (Dexedrine), and 16 with either imipramine or desipramine. The duration of treatment was for a minimum of two years, and averaged five years, with an average follow-up of six years from the onset of treatment. Their weight and height had been measured prior to treatment, and these and subsequent measurements were converted to percentiles, using the tables of norms of the Iowa City study. Initially there was a diminution in expected weight, but not height, but after a few years the growth in weight and height was found to be greater than predicted from the norms to a statistically significant degree. Gains in weight and height were greater for those whose medication had been stopped prior to the final measurements than for those still taking medication; but these differences did not reach statistical significance. No correlations were found between dosage level and changes in weight and height percentiles. It is concluded that there is no stunting of growth from the long-term use of methylphenidate, dextroamphetamine, or imipramine/desipramine in children. Any slowing of growth when treatment is first started is compensated for later on, both while the patient is still taking the medication, and after discontinuing it.

Adolescent

Hyporesponsivity of chronic schizophrenic patients to dextroamphetamine.

Among the evidence supporting the dopamine hypothesis of schizophrenia is the finding that both amphetamine and methylphenidate hydrochloride, potent releasers of dopamine, can cause exacerbation of symptoms in the acute schizophrenic patient. The present report describes three experiments in which the effects of amphetamine in chronic schizophrenic patients were studied. In one of the experiments, orally administered, daily doses of 20 mg of dextroamphetamine sulfate given at 8 PM had little or no effect on the sleep duration of the subjects. In the other two experiments, doses up to 40 mg given orally also had little or no effect on the performance of the subjects on a variety of behavioral tests. There was no evidence of an exacerbation of the disease process in any of the subjects. The most consistent amphetamine effect was a dose-related increase in blood pressure. These results indicate that the chronic schizophrenic patient may be hyporesponsive to amphetamine and suggest that if the dopamine hypothesis is correct, then it must be modified to take into account these findings in the chronic patient.

Adult

Effects of marihuana-dextroamphetamine combination.

Under a double blind, randomized, complete block design, subjects were given either placebo and 10 mg/70 kg dextroamphetamine sulfate (A) orally followed 1 1/2 hr later by a marihuana cigarette (M) prepared to deliver 50 mug/kg delta-9-tetrahydrocannabinol (THC). Statistical analyses suggested that heart rate and blood pressure increased in an additive manner when both drugs were given. Electrocardiogram changes, when present, were nonspecific in character and appeared to be associated with marihuana. In a second study, psychomotor performance was evaluated by a similar design using doses of 10 mg/70 kg of A and M prepared to deliver 25 mug/kg THC. Impairment was related to smoking of M, and no difference could be distinguished between M alone and M-A combination. Subjective evaluation, as measured by the modified Cornell Medical Index (CMI) demonstrated only additive effects for the combination.

Adult