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PubMed1976

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↗
PubMed1977

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↗
PubMed1995

Comparative abuse liability of sertraline, alprazolam, and dextroamphetamine in humans.

Sertraline is an effective antidepressant acting as a selective serotonin reuptake inhibitor. The subjective and behavioral effects of sertraline were studied and compared with the effects of alprazolam and dextroamphetamine in a within-subject, randomized, double-blind study in 20 volunteers aged 18 to 46 years. These subjects were experienced but nondependent users of central nervous system depressants who had the ability to reliably distinguish secobarbital, 150 mg, from placebo and to report positive subjective effects of secobarbital in an experimental setting. The following drug conditions were tested: sertraline, 100 and 200 mg; alprazolam, 1 mg; dextroamphetamine, 10 mg; and placebo. Drug effects were assessed with an objective test of psychomotor performance, subject-rated questionnaires, and observer-rated scales. Both alprazolam and dextroamphetamine were distinguishable from placebo on most measures, but sertraline produced effects discernable from placebo on only a few measures. At 1 hour postdrug administration, dextroamphetamine and alprazolam produced positive effects on several measures of elation, euphoria, and drug liking greater than placebo and both doses of sertraline. In contrast, sertraline produced higher scores on measures of dysphoria and physical unpleasantness than did the other drug conditions. Observer ratings of satisfaction with the drug and other pharmacologic effects were consistent with these findings. Results from this study indicate that sertraline, at the doses tested, does not possess the behavioral effects profile considered to be indicative of abuse potential when compared with alprazolam and dextroamphetamine.

1-Naphthylamine↗
PubMed1997

Diltiazem, a calcium antagonist, partly attenuates the effects of dextroamphetamine in healthy volunteers.

Calcium antagonists have previously been shown to be effective in the treatment of mania. In the present study we used dextroamphetamine administered to humans as a model of mania, to determine whether the calcium antagonist diltiazem would prevent dextroamphetamine-induced changes. This may help determine whether diltiazem is likely to be useful in the treatment of mania. Ten healthy volunteers were enrolled in this double-blind, placebo-controlled, balanced crossover study. Subjects received either oral diltiazem (60 mg) and placebo, placebo and dextroamphetamine (20 mg), diltiazem and dextroamphetamine, or placebo alone. Subjective and sleep changes were measured using visual analogue scales. Attentiveness and visual reaction times were measured repeatedly as were diastolic and systolic blood pressure. The results showed that dextroamphetamine alone produced a number of subjective changes, cardiovascular changes and changes in reaction time. Diltiazem significantly attenuated the cardiovascular changes, but not the subjective or reaction time changes. It is hypothesized that these findings may represent effects of diltiazem on noradrenergic neurotransmission. The results are tentatively supportive of suggestions that diltiazem may be clinically useful in the treatment of mania, as is another calcium channel antagonist, verapamil.

Adult↗
PubMed2000

Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.

BACKGROUND: This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with medical illness and an uncertain, but limited, life expectancy. METHOD: Primary inclusion criteria included the presence of a DSM-IV depressive disorder, debilitating fatigue, and no history of dependence on stimulants. The study consisted of a 2-week randomized, placebo-controlled trial, with the blind maintained until week 8 for responders, followed by open treatment through the completion of 6 months. RESULTS: Of 23 men who entered the study, 22 completed the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11) randomly assigned to dextroamphetamine reported significant improvement in mood and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p < .05). Both clinician- and self-administered measures indicated significantly improved mood, energy, and quality of life among patients taking dextroamphetamine. There was no evidence of the development of tolerance of, abuse of, or dependence on the medication. CONCLUSION: These results suggest that dextroamphetamine is a potentially effective, fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue.

Adult↗
PubMed2004

Dextroamphetamine use during B-2 combat missions.

INTRODUCTION: Fatigue among warriors can jeopardize mission success. Prescribed stimulant medications, in-flight sleep, and self-medication with caffeine can mitigate fatigue. During Operation Iraqi Freedom, pilots flew the B-2 bomber to targets in Iraq from one of two airfields. Sortie durations were long (16.9 h) from one field and very long (35.3 h) from the other. Controversy exists concerning the use of stimulant medication, in part because of a paucity of combat data. METHODS: A retrospective analysis of 75 pilots who performed 94 combat sorties was performed. We examined the prevalence of the pilot's decision to use dextroamphetamine, caffeine, and in-flight sleep during combat. We compared demographic factors, the impact of one anti-fatigue tool on the use of others, stimulant benefit, and adverse effects. RESULTS: Pilots on shorter missions used dextroamphetamine for 97% and in-flight naps for 13% of sorties. Those on longer missions used dextroamphetamine on 58% and naps on 94% of sorties. Stimulant use was not affected by pilot age, bomber experience, or long-duration experience. The opportunity to obtain in-flight sleep was limited by certain mission profiles, which influenced the decision to use dextroamphetamine. Among pilots who used the medication, 97% noted a benefit. Side effects and failure to observe benefits were uncommon. CONCLUSIONS: B-2 pilots in long-duration combat flight selectively employ dextroamphetamine, naps, and other fatigue countermeasures. Major determinants of these decisions are mission requirements and the pilot's experience with each measure and its effect.

Adult↗
PubMed2002

The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma.

BACKGROUND: Obesity and attention difficulties are known complications following surgical treatment for craniopharyngioma. Treatments to date have been largely disappointing. OBJECTIVE: To examine the use of the central nervous system stimulant dextroamphetamine sulfate to regulate appetite and subsequent weight gain in children treated for craniopharyngioma. SETTING: A multidisciplinary clinic specializing in pediatric brain tumors. PATIENTS: Five consecutive patients with significant weight gain and poor attention following surgical treatment for craniopharyngioma were selected for the study. INTERVENTION: Children enrolled in the study were treated with dextroamphetamine, and growth, laboratory, and behavioral assessments were conducted for 24 months. RESULTS: Mean +/- SD body mass index (weight in kilograms divided by height in meters squared) increased from 21 +/- 3.5 before the operation to 32 +/- 2.8 by the start of the protocol. Body mass indices remained stable throughout the protocol. No changes were observed in insulin levels or caloric intake, but the children were more active when taking dextroamphetamine. Parents noted a significant improvement in hyperactivity (mean +/- SD, 1.2 +/- 0.4 to 0.6 +/- 0.2; P =.05), scored with the Conners Parent and Teacher Rating Scales. Teachers noted a similar improvement. CONCLUSIONS: During dextroamphetamine treatment, weight gain stabilized in children who had experienced obesity following surgical resection for craniopharyngioma. In addition, parents and teachers noted significant improvements in children's overall activity and attention. Further studies are needed to determine if the improvements are stable and if earlier intervention can prevent the initial obesity.

Analysis of Variance↗
PubMed1989

Fenfluramine and dextroamphetamine treatment of childhood hyperactivity. Clinical and biochemical findings.

Twenty boys (mean age, 9 +/- 2 years) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate (0.5 mg/kg/d), fenfluramine hydrochloride (0.6 mg/kg/d increased to 2.0 mg/kg/d), and placebo in a double-blind, random-order, crossover design. Half the boys also met criteria for conduct disorder. Dextroamphetamine produced immediate and marked improvement in disruptive, overactive behaviors. Fenfluramine had no effect on any behavioral measure at either the low or high dosage. Both drugs decreased levels of urinary norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid. Fenfluramine, however, also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels. It reduced urinary epinephrine levels as well, an effect opposite to that of dextroamphetamine. These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylmandelic acid. Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels. Despite the structural similarity of the two drugs, some common overall effects on catecholamine metabolism, and similar effects on weight, fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers.

An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of modafinil, the acid and sulfone metabolites of modafinil, and dextroamphetamine at intervals through 48 hours after administration for each treatment. Vital signs (blood pressure and pulse rate) were measured through 48 hours, and electrocardiograms were measured through 24 hours after administration. Pharmacokinetic parameters were determined using noncompartmental methods. The data collected in this study of 24 healthy volunteers suggest that concomitant administration of single oral doses of modafinil and dextroamphetamine has no clinically significant effects on the pharmacokinetic profile of either agent. Although there was a slightly greater incidence of adverse events when modafinil and dextroamphetamine were administered together, the concomitant administration of the two drugs was well tolerated.

Adult↗
PubMed1984

Separate mechanisms for behavioral, cardiovascular, and hormonal responses to dextroamphetamine in man.

The neurochemical specificity of physiological, biochemical, and psychological responses to dextroamphetamine was tested by pretreating volunteers with haloperidol (0.014 mg/kg IM), propranolol (0.1 mg/kg IV), thymoxamine (0.1 mg/kg IV), or placebo prior to 0.3 mg/kg IV amphetamine. Healthy volunteers (N = 12) participated in the studies, but not all volunteers received each drug combination. Haloperidol prevented dextroamphetamine-induced behavioral excitation, but did not significantly affect plasma norepinephrine or pressor responses, whereas propranolol inhibited norepinephrine and pressor responses without influencing excitation or other behavioral responses. Thymoxamine did not affect any of the responses measured. None of the agents significantly affected plasma cortisol or growth hormone responses. The prolactin rise following dextroamphetamine was potentiated by haloperidol. The results are consistent with the hypothesis that behavioral excitation after dextroamphetamine occurs through a dopaminergic mechanism, and pressor responses through a noradrenergic mechanism.

Adult↗
PubMed1987

Effects of chronic administration of dextroamphetamine on enzymes of energy metabolism in regions of the rat brain.

In the present study the effects of chronic administration of dextroamphetamine on energy metabolism in the brain of the rat were examined. The enzymes studied were: hexokinase (soluble and particulate forms), phosphofructokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase, NAD+ and NADP+-dependent isocitrate dehydrogenases, succinate dehydrogenase and malate dehydrogenase. All the activities of the enzymes were assayed in four regions of the brain of the rat (cerebellum, medulla oblongata and pons, cererbral cortex and diencephalon). Rats were injected intaperitoneally once daily with dextroamphetamine for 20 consecutive days. The initial dose was 5 mg/kg/day and the dose was then increased by 1 mg/kg/every 5 days up to a total of 8 mg/kg/day on days 16-20. In the glycolytic enzymes a reduction of the activity of phosphofructokinase was found in the diencephalon and an increase of the activity of pyruvate kinase and lactate dehydrogenase in the diencephalon and medulla oblongata and pons, respectively. Citrate synthase was the only enzyme in the Krebs' cycle affected by chronic administration of dextroamphetamine. The results presented here show that chronic administration of dextroamphetamine produced important changes in some enzymes of glycolysis and the Krebs' cycle in the brain of the rat.

Animals↗
PubMed1987

Modulation of dopamine receptors in the Tapes clam by dextroamphetamine and phenylethanolamine.

The mechanism underlying the modulation, by dextroamphetamine and compounds related to phenylethanolamine, of responses to dopamine and serotonin has been studied in the isolated ventricle and aortic bulb of the clam Tapes watlingi. Dextroamphetamine and phenylethanolamine but not cocaine and benztropine have the ability to unmask inhibitory responses to both dopamine and serotonin in the ventricle. Chlordimeform but not clozapine attenuates the inhibitory response to both dextroamphetamine and phenylethanolamine in concentrations which have little or no effect on the inhibitory response to dopamine in the ventricle. Phenylethanolamine, dextroamphetamine, phenylpropylolamine and p-chloro-phenylethanolamine but not octopamine or noradrenaline attenuate the contractile responses to both dopamine and serotonin in preparations of the quiescent aortic bulb. These data show that there are specific receptors for phenylethanolamine in the Tapes heart capable of modulating responses to dopamine and serotonin, and suggests that this biogenic phenethylamine can act as an environmental and physiological factor which may determine how the mollusc heart responds to dopamine.

Adenosine Monophosphate↗
PubMed1989

Differential effects of methylphenidate and dextroamphetamine on the motor activity level of hyperactive children.

An acceleration-sensitive device was used to measure motor activity continuously through the day in 18 hyperactive boys in a day hospital program. The children received methylphenidate, dextroamphetamine, or placebo daily after breakfast and lunch in an 11-week double-blind crossover trial. Differential effectiveness of the two drugs in lowering motor activity was found. Methylphenidate significantly lowered activity measurements in a morning structured classroom and in less structured activities in the afternoon. Dextroamphetamine effects on activity were similar, although they did not differ significantly from placebo effects between 11:00 AM and noon in our classroom setting. Methylphenidate produced a greater decrement in motor activity than did dextroamphetamine between 11:00 AM and 1:00 PM. There were no significant differences in activity level between drug doses within each drug phase across the dose ranges used (for methylphenidate 0.45 to 1.25 mg/kg given twice daily, and for dextroamphetamine 0.2 to 0.6 mg/kg given twice daily). Plasma drug concentrations did not correlate with decrements in activity for either drug.

Child↗
PubMed1977

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↗
PubMed1997

Intravenous dextroamphetamine and brain glucose metabolism.

This study reports the effects of intravenous dextroamphetamine on cerebral glucose metabolism assayed by positron emission tomography (PET) and [fluorine-18]fluorodeoxyglucose (FDG) in 13 healthy adults during the performance of a continuous visual attention task. Two FDG PET scans were performed within a single experimental session. The first scan was preceded by the injection of placebo and the second scan by the injection of 0.15 mg/kg dextroamphetamine. Global and normalized regional glucose metabolic rates (rCMRglc) were examined as a function of pharmacological challenge and subjective experience. Subcortical, limbic, frontal, and cerebellar rCMRglc significantly increased after dextroamphetamine, whereas rCMRglc of the temporal cortex significantly decreased. Physiological and self-report measures of subjective states showed the expected alterations. These rCMRglc changes reflect both the direct pharmacological effect of dextroamphetamine on monoaminergic neurotransmitter systems as well as enhancement of the activation of the neural network mediating the performance of the continuous attention task.

Adult↗
PubMed2005

Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation.

Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with dextroamphetamine on others. At the doses tested, caffeine, dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear.

Adult↗
PubMed1994

Effects of intravenous dextroamphetamine on brain metabolism in adults with attention-deficit hyperactivity disorder (ADHD). Preliminary findings.

The effects on brain metabolism of the intravenous (i.v.) administration of dextroamphetamine was assessed by positron emission tomography (PET) with [18F]-fluorodeoxyglucose (18-FDG) in 8 adults with attention-deficit hyperactivity disorder (ADHD). During the 3-hour 18-FDG PET session, each adult underwent the initial scan following i.v. infusion of placebo and a second scan following i.v. infusion of 0.15 mg/kg dextroamphetamine in a single-blind design. All subjects showed increased systolic/diastolic blood pressure and improved continuous performance task scores after dextroamphetamine. Global and regional metabolic rates were not significantly altered by the stimulant. When regional and global rates were normalized, the metabolic rates of only three cortical regions differed significantly between conditions. Individually, global metabolism increased in 4 subjects, was unchanged in 2, and decreased in 2 after stimulant infusion. No clinical characteristics differentiated these patients. I.V. infusion of dextroamphetamine did not significantly alter brain metabolism in ADHD adults in this preliminary study.

Adult↗
PubMed1996

Effects of operationally effective doses of dextroamphetamine on heart rates and blood pressures of army aviators.

The cardiovascular effects of 30 mg of dextroamphetamine, given in divided 10-mg doses at midnight, 4 a.m., and 8 a.m. during a sustained-operations scenario, were explored. Blood pressures and heart rates of male and female UH-60 pilots were measured during two periods of continuous wakefulness in which subjects received dextroamphetamine and placebo. Persistent elevations in heart rates were observed from 2 hours after the second 10-mg dose of dextroamphetamine until the end of the day. Systolic blood pressures of males were elevated from 1 hour after the first 10-mg dose until 5 hours after the third 10-mg dose. Systolic blood pressures of females increased 1 hour after the third 10-mg dose of dextroamphetamine and remained high until 6 hours after the third 10-mg dose. Diastolic blood pressures in both genders showed a persistent elevation from 2 hours past the second 10-mg dose until 6 hours after the third 10-mg dose. These changes did not result in any clinically detectable adverse sequelae.

Adult↗