Dextroamphetamine, catecholamines, and behavior. The effect of dextroamphetamine in retarded children.
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Catecholamines↗
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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↗
A randomized double-blind trial of paroxetine and/or dextroamphetamine and problem-focused therapy for attention-deficit/hyperactivity disorder in adults.
OBJECTIVE: To determine the effect of psychotherapy, dextroamphetamine, and/or paroxetine on attention-deficit/hyperactivity-disorder (ADHD) in adults. METHOD: Ninety-eight adults with DSM-IV ADHD were randomly assigned to receive psychotherapy and dextroamphetamine, paroxetine, both, or placebo for 20 weeks. A 2 x 2 factorial design compared patients who received dextroamphetamine versus no dextroamphetamine with patients who received paroxetine versus no paroxetine. Data were collected from August 2000 until May 2002. RESULTS: One half of the 98 enrolled subjects were found to have at least 1 lifetime mood or anxiety disorder on the Structured Clinical Interview for DSM-IV. Sixty percent of patients who received medication and 80% of those who received placebo completed the 5-month trial. ADHD symptoms were significantly (p = .012) lower in patients in the completer group who received dextroamphetamine. Paroxetine had no effect on ADHD. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) scores were low to start, and no treatment differences were evident at endpoint. Significantly (p < .001) more patients in the completer group were rated by clinicians as ADHD responders if they received dextroamphetamine (85.7%) or combined treatment (66.7%) versus paroxetine (20.0%) or placebo (21.1%). Significantly (p = .003) more patients in the completer group were rated by clinicians as mood/anxiety responders if they received paroxetine (100%) or combined treatment (73.3%) versus those receiving dextroamphetamine (57.15%) or placebo (47.4%). Clinicians rated any patient who received medication and psychological therapy as significantly more improved overall than those who received placebo and psychological therapy (intent to treat: p = .033; completers: p = .001). CONCLUSION: ADHD symptoms improved with dextroamphetamine. Mood and internalizing symptoms were seen as improved with paroxetine by clinicians, despite absence of response on the HAM-A and HAM-D. The presence of a lifetime internalizing disorder attenuated the response to dextroamphetamine. Patients who received both dextroamphetamine and paroxetine had more severe adverse events but did not show greater improvement overall than patients treated with 1 medication. Clinical Trials Registry #GSK707.
Adult↗
Comparison of methods for the assessment of central nervous system stimulant response after dextroamphetamine administration to healthy male volunteers.
The objective of this investigation was to evaluate a series of potential pharmacodynamic measures of central nervous system stimulation, including quantitative electroencephalography (EEG) and neuroendocrine, mood, and psychomotor performance measures. The reproducibility and sensitivity of the measures were compared. The study was conducted in two parts. The first part investigated the interindividual and intraindividual variability associated with a series of potential pharmacologic response measures under baseline (i.e., drug-free) conditions. It was an open-label, three-period pilot study in which healthy male volunteers underwent a series of tests (EEG, a visual continuous performance task, a finger tapping task, and self-rated mood scales) repeatedly during each study period. The second part evaluated the sensitivity of a series of potential response measures to detect the effects of dextroamphetamine, and was a double-blind, placebo-controlled, four-period crossover study in nine healthy male volunteers. Subjects received 5 mg, 10 mg, or 20 mg of dextroamphetamine or placebo orally and underwent the same series of tests as in Part I in addition to blood collection for determination of serum prolactin and dextroamphetamine levels. Peripheral response to dextroamphetamine was assessed by heart rate and blood pressure measurement. The greatest variability among days, within days, and among participants was associated with the quantitative electroencephalographic parameters studied. First-session effects were apparent for several of the tests, including EEG. Consistent response on EEG (increased alpha power) to dextroamphetamine was observed only in the three subjects who had a baseline alpha activity greater than 35%. Serum prolactin levels were inversely associated with the amount of dextroamphetamine administered, with the largest decrease in serum prolactin levels observed after the 5-mg dose, and this finding was statistically significant. Mood scales showed that three of nine participants experienced dysphoria after at least one dose level of dextroamphetamine. The effect on mood was generally greater as the dose increased. Doses could not be distinguished based on the results of the performance tests. Serum prolactin concentration was the most sensitive measure of central nervous system stimulation on EEG produced by dextroamphetamine under these study conditions. Cardiovascular measures were more sensitive measures of dextroamphetamine effects than the central nervous system measures.
Adult↗
Long-term pimozide pretreatment differentially affects behavioral responses to dextroamphetamine in schizophrenia. Further exploration of the dopamine hypothesis of schizophrenia.
In ten of 30 schizophrenic patients treated with pimozide for five weeks, 20 mg of dextroamphetamine sulfate induced an increase in psychosis. The number of patients becoming more psychotic with the dextroamphetamine challenge was not significantly different from the number who worsened after dextroamphetamine challenge when pretreated with placebo. Half of the patients who showed a psychotic response to dextroamphetamine during placebo pretreatment responded to dextroamphetamine with an increase in psychosis after pimozide treatment. Dextroamphetamine induced a worsening in patients who had improved with pimozide. The stability of the preinfusion condition is more important to the type of response to dextroamphetamine than long-term pretreatment with a dopamine receptor blocker. The activation-euphoria response to dextroamphetamine was unaffected by pimozide pretreatment, which suggests that the changes in psychosis and activation may be regulated by different mechanisms. These findings question the postulated relationship between the antipsychotic drug response and dopamine receptor blockade.
Adolescent↗
Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study.
Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine.
Adult↗
Lithium and valproate attenuate dextroamphetamine-induced changes in brain activation.
BACKGROUND: Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI-cycle) activity. There is also evidence that dextroamphetamine may increase PI cycle activity. It was previously demonstrated that dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these dextroamphetamine-induced changes in regional brain activity in healthy volunteers. METHODS: This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9) or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after administration of dextroamphetamine (25 mg). Changes in the number of activated pixels and changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after dextroamphetamine administration were then determined. RESULTS: In keeping with previous findings dextroamphetamine administration decreased regional brain activation in all three tasks. Pretreatment with lithium attenuated changes in the word generation paradigm and the spatial attention task, while pretreatment with valproate attenuated the changes in the working memory task. CONCLUSIONS: These results suggest that both lithium and valproate can significantly attenuate dextroamphetamine-induced changes in brain activity in a task dependent and region specific manner. This is the first human evidence to suggest that both lithium and valproate may have a similar effect on regional brain activation, conceivably via similar effects on PI-cycle activity.
Adult↗
Effects of dextroamphetamine on cognitive performance and cortical activation.
Monoaminergic neurotransmitters are known to have modulatory effects on cognition and on neurophysiological function in the cortex. The current study was performed with BOLD fMRI to examine physiological correlates of the effects of dextroamphetamine on working-memory performance in healthy controls. In a group analysis dextroamphetamine increased BOLD signal in the right prefrontal cortex during a task with increasing working-memory load that approached working-memory capacity. However, the effect of dextroamphetamine on performance and on signal change varied across individuals. Dextroamphetamine improved performance only in those subjects who had relatively low working-memory capacity at baseline, whereas in the subjects who had high working-memory capacity at baseline, it worsened performance. In subjects whose performance deteriorated, signal change was greater than that in subjects who had an improvement in performance, and these variations were correlated (Spearman rho = 0.89, P<0.02). These data shed light on the manner in which monoaminergic tone, working memory, and prefrontal function interact and, moreover, demonstrate that even in normal subjects the behavioral and neurophysiologic effects of dextroamphetamine are not homogeneous. These heterogeneic effects of dextroamphetamine may be explained by genetic variations that interact with the effects of dextroamphetamine.
Adult↗
Valproate attenuates dextroamphetamine-induced subjective changes more than lithium.
Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.
Adolescent↗
Dextroamphetamine pilot crossover trials and n of 1 trials in patients with chronic tension-type and migraine headache.
OBJECTIVE: To examine the preventive effects of dextroamphetamine in select small groups of patients with chronic tension-type and migraine headache. BACKGROUND: Neither amphetamine nor methylphenidate is used as a headache preventive. This study was undertaken after a chance observation led one of us to prescribe dextroamphetamine with apparent successes in specific patients with chronic tension-type or migraine headaches. METHODS: Two pilot trials were done. Trial 1 tested patients who were taking dextroamphetamine, while Trial 2 tested patients who had never taken this drug. Each trial obtained full data on eight subjects with chronic tension-type headache and eight subjects with migraine headache. A randomized, double-blinded, controlled, multiple-crossover design was used. Subjects took capsules containing dextroamphetamine or equi-stimulatory caffeine (the control) during four alternating 20-day periods. Trial 1 subjects took their pretrial dextroamphetamine dose at breakfast and lunch. Trial 2 subjects took 10 mg at these times. Subjects recorded the integer from 0 to 3 that represented their headache intensity during the previous 24 hours. The subject's data were the average daily headache grade for the two dextroamphetamine periods and for the two caffeine periods. The differential effect of amphetamine and caffeine on each group of eight subjects and on each individual was analyzed by t-tests. RESULTS: In both trials, the tension-type and migraine groups had lower mean daily headache grades in the amphetamine than in the caffeine periods. P values for these differences indicated that there were real drug effects, on the average, in the migraine groups (P<.05) and suggestive but inconclusive effects in the tension-type groups (P<.10). The individual n of 1 analyses showed that five tension-type and three migraine subjects in Trial 1 and three tension-type and three migraine subjects in Trial 2 had considerably lower mean daily headache grades on amphetamine with P values indicating, at various levels of significance (from P<.05 to P<.001), real amphetamine effects. Twelve of the remaining 18 patients had lower, albeit not significant, mean daily grades with amphetamine. No subject in either trial had a significantly lower mean daily headache grade on caffeine. CONCLUSIONS: Dextroamphetamine had real preventive effects on chronic tension-type and migraine headaches in some subjects. These results should encourage other investigators to study its effects on these headaches.
Adolescent↗
Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine.
BACKGROUND: The state of the brain reward system in major depressive disorder was assessed with dextroamphetamine, which probes the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, and produces measurable behavioral changes, including rewarding effects (eg, euphoria). We hypothesized that depressed individuals would exhibit an altered response to dextroamphetamine due to an underlying brain reward system dysfunction reflected by anhedonic symptoms. METHODS: In a double-blind, placebo-controlled, randomized, parallel study, the behavioral and physiological effects of a single 30-mg dose of oral dextroamphetamine sulfate were measured. Forty patients with a diagnosis of DSM-IV major depressive disorder who were not taking antidepressant medications (22 assigned to dextroamphetamine and 18 to placebo) were compared with 36 control subjects (18 assigned to dextroamphetamine and 18 to placebo) using validated self-report drug effect measurement tools (eg, the Addiction Research Center Inventory), heart rate, and blood pressure. RESULTS: Multiple regression analysis showed that severity of depression as measured by the Hamilton Rating Scale for Depression correlated highly with the rewarding effects of dextroamphetamine in the depressed group (model R(2) = 0.63; interaction P =.04). A subsequent analysis categorizing the depressed group into patients with severe symptoms (Hamilton score >23) and those with moderate symptoms revealed a significant interaction between drug and depression (P =.02). Patients with severe symptoms reported rewarding effects 3.4-fold greater than controls. CONCLUSIONS: The results suggest the presence of a hypersensitive response is present in the brain reward system of depressed patients, which may reflect a hypofunctional state and may provide a novel pathophysiologic and therapeutic target for future studies.
Adult↗
Dextroamphetamine with morphine: respiratory effects.
The combination of dextroamphetamine and morphine has been shown to be synergistic for analgesia and antagonistic for most other effects. However, the claim that dextroamphetamine antagonizes the respiratory depression caused by morphine has not been well substantiated. In this double-blind study, we investigated respiratory effects, including resting respiration, isohypercapnic ventilation, CO2 response, dose response, and duration of these effects with dextroamphetamine alone and in combination with morphine. Dextroamphetamine alone (0.215 mg/kg) caused increases in minute ventilation and a leftward shift of the CO2 response curve that lasted for less than 2 hours. Dextroamphetamine combined with low-dose morphine (0.15 mg/kg) antagonized respiratory depression throughout the 5-hour observation period. Dextroamphetamine combined with high-dose morphine (0.30 mg/kg) was unable to completely antagonize depressed ventilation, and some residual effects of morphine persisted at 23 hours.
Carbon Dioxide↗
Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks: a functional magnetic resonance imaging study of blood oxygen level-dependent response.
BACKGROUND: Dextroamphetamine is known to have profound effects on both subjective and physiologic measurements, but it is unclear to what extent these behavioral changes are a direct result of altered regional brain activation. One method to measure this is to use functional magnetic resonance imaging (fMRI). METHODS: In the present study, fMRI was used to measure both the spatial extent of changes (the number of pixels activated) and the magnitude of the blood oxygen level-dependent (BOLD) response. We examined the effects of motor, verbal, memory, and spatial attention task during fMRI in 18 healthy volunteers. Functional MRI measurements were obtained at baseline and again 75 min after an oral dose of 25 mg dextroamphetamine. RESULTS: Dextroamphetamine caused a decrease in the number of activated pixels and the magnitude of the BOLD response during the three cognitive tasks tested but not during the motor task. These changes were region and task specific. CONCLUSIONS: This is the first study to examine the effect of dextroamphetamine on the number of activated pixels and the BOLD response during the performance of a range of cognitive and motor tasks. Our results suggest that dextroamphetamine causes measurable decreases in brain activity in a variety of regions during cognitive tasks. These changes might be linked to behavioral changes observed after dextroamphetamine administration and could possibly be mediated by alterations in dopaminergic activation.
Adult↗
Recovery sleep and performance following sleep deprivation with dextroamphetamine.
Twelve subjects were studied to determine the after-effects of using three 10-mg doses of dextroamphetamine to sustain alertness during sleep deprivation. Sleep architecture during recovery sleep was evaluated by comparing post-deprivation sleep after placebo. Performance and mood recovery were assessed by comparing volunteers who received dextroamphetamine first (during sleep deprivation) to those who received placebo first. Stages 1 and 2 sleep, movement time, REM latency, and sleep latency increased on the night after sleep deprivation with dextroamphetamine vs. placebo. Stage 4 was unaffected. Comparisons to baseline revealed more stage 1 during baseline than during either post-deprivation sleep period and more stage 2 during baseline than during sleep following placebo. Stage 4 sleep was lower during baseline and after dextroamphetamine than after placebo. Sleep onset was slowest on the baseline night. Next-day performance and mood were not different as a function of whether subjects received dextroamphetamine or placebo during deprivation. These data suggest dextroamphetamine alters post-deprivation sleep architecture when used to sustain alertness during acute sleep loss, but next-day performance and subjective mood ratings are not substantially affected. A recovery sleep period of only 8 h appears to be adequate to regain baseline performance levels after short-term sleep deprivation.
Adult↗
Effects of dextroamphetamine, lithium chloride, sodium valproate and carbamazepine on intraplatelet Ca2+ levels.
OBJECTIVE: To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we investigated the effects of dextroamphetamine (a model for mania) and the most widely used mood stabilizers, lithium chloride, sodium valproate and carbamazepine, on intraplatelet levels of calcium ion ([Ca2+). DESIGN: In the first part of the study, dextroamphetamine was administered in vivo in a double-blind, placebo-controlled, crossover design. In the second part of the study, platelets from untreated subjects were incubated in vitro with dextroamphetamine, lithium chloride, sodium valproate or carbamazepine. PARTICIPANTS: Fifteen healthy men between 18 and 45 years of age. OUTCOME MEASURES: Basal, thrombin-induced and serotonin- (5-HT) induced intraplatelet [Ca2+] determined by means of fura-2 fluorescent intensity. RESULTS: In vivo administration of dextroamphetamine had no effect on basal or agonist-induced intraplatelet [Ca2+]. However, in vitro basal platelet [Ca2+] was significantly higher in samples incubated with dextroamphetamine (86.8 nmol/L [standard error of the mean, SEM, 3.9], p < 0.001), lithium chloride (76.4 nmol/L [SEM 3.1], p < 0.002), sodium valproate (82.7 nmol/L [SEM 3.7], p < 0.001) and carbamazepine (84.8 nmol/L [SEM 3.3], p < 0.001) than in the controls (58.2 nmol/L [SEM 2.3]). Thrombin-induced and 5-HT-induced peak cytosolic [Ca2+] were significantly greater than control levels in samples incubated with carbamazepine (277.1 nmol/L [SEM 19.9] v. 195.8 nmol/L [SEM 12.2], p < 0.002; and 153.0 nmol/L [SEM 8.2] v. 115.4 nmol/L [SEM 5.7], p < 0.003, respectively). CONCLUSIONS: This study does not support the involvement of intraplatelet [Ca2+] in the dextroamphetamine model of mania; however, the modulation of intraplatelet [Ca2+] by the mood stabilizers lithium chloride, sodium valproate and carbamazepine implicates intracellular [Ca2+] in the therapeutic mechanisms of these drugs and the pathophysiological basis of mania.
Adolescent↗
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↗
Stimulants, urinary catecholamines, and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine.
Children with attention deficit disorder with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine sulfate to compare the effects on urinary excretion of catecholamines, indoleamines, and phenylethylamine (PEA). Methylphenidate's effects were distinctly different from those of dextroamphetamine. After methylphenidate administration, both norepinephrine (NE) and normetanephrine (NMN) concentrations were significantly elevated, and there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG). In contrast, after dextroamphetamine treatment, MHPG excretion was significantly reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites was unchanged by either drug. Urinary PEA excretion was not significantly changed after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine. Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic acid excretion. Effects of dextroamphetamine were not tested.
3,4-Dihydroxyphenylacetic Acid↗
Behavioral and neurochemical interactions of dextroamphetamine and methylphenidate in rats.
The effects of dextroamphetamine and methylphenidate on locomotor activity and brain levels of norepinephrine and dopamine were compared in male Sprague-Dawley rats. Both drugs produced a dose-related increase in locomotor activity during the hour immediately following intraperitoneal administration. However, combined administration of drugs elicited only the effect of dextroamphetamine. Brain levels of norepinephrine and dopamine also increased 1 hr after dextroamphetamine dosing. Methylphenidate did not exhibit these effects and antagonized the neurochemical changes produced by dextroamphetamine. Although both drugs are considered to exert their effects by indirect activation of brain catecholamine systems, differences in their mechanism of action appear to result in a lack of additive or antagonistic effects when dextroamphetamine and methylphenidate are coadministered. These findings may have clinical significance with respect to the use of such agents in minimal brain dysfunction.
Aging↗