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Journal of Psychopharmacology (Oxford,... Jun 2013Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range... (Review)
Review
Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.
Topics: Adolescent; Adult; Amphetamine; Amphetamine-Related Disorders; Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Drug Design; Humans; Lisdexamfetamine Dimesylate; Narcolepsy; Prodrugs
PubMed: 23539642
DOI: 10.1177/0269881113482532 -
American Journal of Therapeutics
Topics: Humans; Amphetamine; Salts; Colitis, Ischemic; Dextroamphetamine
PubMed: 32618593
DOI: 10.1097/MJT.0000000000001172 -
CNS & Neurological Disorders Drug... 2023Stroke is a physiological disorder involving a prolonged local interruption of cerebral blood flow. It leads to massive neuronal death and causes short-term or... (Review)
Review
Stroke is a physiological disorder involving a prolonged local interruption of cerebral blood flow. It leads to massive neuronal death and causes short-term or long-lasting functional impairment. Most stroke victims regain some neural function weeks or months following a stroke, but this recovery can plateau six months or more after the injury. The goal of stroke therapy is the rehabilitation of functional capabilities, especially those affecting the patient's autonomy and quality of life. Recent clinical and animal studies combining acute dextro-amphetamine (d-AMPH) administration with rehabilitative training (RT) have revealed that this treatment has significant remedial effects. The review aims to examine the synergistic therapeutic effects of d-amphetamine coupled with RT, administered during the early or late subacute period, on neuronal activation, anatomic plasticity, and skilled motor function in a middle-aged rodent stroke model. The treatment will also include magnetic field stimulation. This review will help increase understanding of the mechanism of d-amphetamine coupled with RT and magnetic field stimulation and their converging therapeutic effects for stroke recovery.
Topics: Animals; Humans; Quality of Life; Neuronal Plasticity; Recovery of Function; Stroke; Brain; Dextroamphetamine; Stroke Rehabilitation
PubMed: 35549868
DOI: 10.2174/1871527321666220512155811 -
American Journal of Pharmacy and the... 1971
Review
Topics: Amphetamine; Animals; Dextroamphetamine; Dogs; Guinea Pigs; Haplorhini; Humans; Mice; Psychoses, Substance-Induced; Rabbits; Rats; Species Specificity; Substance-Related Disorders
PubMed: 5003217
DOI: No ID Found -
British Journal of Pharmacology Sep 2022Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by... (Review)
Review
Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Amphetamine; Animals; Antimanic Agents; Dextroamphetamine; Mania; Rats; Ultrasonics; Vocalization, Animal
PubMed: 33830495
DOI: 10.1111/bph.15487 -
Addiction Biology Jan 2021Cortical neurons oscillate synchronously between the Up and Down state during slow-wave sleep and general anesthesia. Using local-field-potential recording in the rat...
Cortical neurons oscillate synchronously between the Up and Down state during slow-wave sleep and general anesthesia. Using local-field-potential recording in the rat prefrontal cortex (PFC), we have shown that systemic administration of methylphenidate promotes PFC Up states and reduces PFC slow oscillation, suggesting a depolarizing effect of the drug on PFC neurons. Here, we report that systemic injection of d-amphetamine produced similar effects. Our evidence further suggests that norepinephrine (NE) plays a major role in the effects of d-amphetamine since they were mimicked by the NE reuptake inhibitors tomoxetine and nisoxetine and completely blocked by the α receptor antagonist prazosin. The effects of d-amphetamine persisted, however, in the presence of α or β receptor blockade. Experiments with α subtype-selective antagonists further suggest that d-amphetamine's effects depend on activation of central, but not peripheral, α receptors. Unexpectedly, the putative α receptor agonist cirazoline failed to mimic the effects of d-amphetamine. Previous studies suggest that cirazoline is also an antagonist at α receptors. Furthermore, it is a partial, not full, agonist at α and α receptors. Whether or not these properties of cirazoline contribute to its failure to mimic d-amphetamine's effects remains to be determined. Methylphenidate and d-amphetamine are two most common medications for attention-deficit/hyperactivity disorder (ADHD). Both, however, are associated with adverse effects including abuse potential and psychotomimetic effects. Further understanding of their mechanisms of action will help develop safer treatments for ADHD and offer new insights into drug addiction and psychosis.
Topics: Amphetamine; Animals; Atomoxetine Hydrochloride; Dextroamphetamine; Dopamine; Male; Methylphenidate; Neurons; Norepinephrine; Prazosin; Prefrontal Cortex; Rats; Receptors, Adrenergic
PubMed: 32003119
DOI: 10.1111/adb.12879 -
Journal of Analytical Toxicology Feb 2022Amphetamine is frequently detected in forensic toxicological cases. Differentiating between the two isomers of amphetamine (d-amphetamine and l-amphetamine) and...
Amphetamine is frequently detected in forensic toxicological cases. Differentiating between the two isomers of amphetamine (d-amphetamine and l-amphetamine) and determining their relative proportion are fundamental to correctly interpret the results of toxicological analyses. The aim of this study was to examine the profile of amphetamine as well as storage stability of the isomers in authentic samples from patients chronically treated with lisdexamfetamine (LDX), the most prescribed medical amphetamine product in Sweden. Blood and urine samples were collected from 18 patients. The samples were analyzed with an achiral (racemate) method for quantification of amphetamine and with a chiral method to determine the proportion of each isomer of amphetamine. The median daily dose of LDX was 40 mg (range, 20-70 mg). The median amphetamine concentration was 0.06 µg/g (range, 0.02-0.15 µg/g) in blood and 6 µg/mL (range, 1-22 µg/mL) in urine. Only d-amphetamine was found in the blood and urine samples from the included patients. Furthermore, no formation of l-amphetamine occurred during the storage for 3 months at 4°C, 9 months at -20°C and three freeze-thaw cycles. The results from this study may be helpful in the interpretation of whether the source of identified amphetamine in biological samples is from LDX drug intake or not.
Topics: Amphetamine; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Sweden
PubMed: 33216112
DOI: 10.1093/jat/bkaa170 -
Sleep Apr 1993
Topics: Amphetamines; Arousal; Dextroamphetamine; Drug Administration Schedule; Drug Prescriptions; Drug Tolerance; Female; Humans; Male; Narcolepsy; Sleep; United Kingdom
PubMed: 8506451
DOI: 10.1093/sleep/16.3.201 -
Neuropharmacology Dec 2014Lisdexamfetamine dimesylate (LDX) is a novel pro-drug of d-amphetamine that is currently used for the treatment of attention-deficit/hyperactivity disorder in children... (Review)
Review
Lisdexamfetamine dimesylate (LDX) is a novel pro-drug of d-amphetamine that is currently used for the treatment of attention-deficit/hyperactivity disorder in children aged ≥ 6 years and adults. LDX is enzymatically cleaved to form d-amphetamine following contact with red blood cells, which reduces the rate of appearance and magnitude of d-amphetamine concentration in the blood and hence the brain when compared with immediate-release d-amphetamine at equimolar doses. Thus, the increase of striatal dopamine efflux and subsequent increase of locomotor activity following d-amphetamine is less prominent and slower to attain maximal effect following an equimolar dose of LDX. Furthermore, unlike d-amphetamine, the pharmacodynamic effects of LDX are independent of the route of administration underlining the requirement to be hydrolyzed by contact with red blood cells. It is conceivable that these pharmacokinetic and pharmacodynamic differences may impact the psychostimulant properties of LDX in the clinic. This article reviews the preclinical pharmacokinetics, pharmacology, and toxicology of LDX. This article is part of the Special Issue entitled 'CNS Stimulants'.
Topics: Animals; Brain; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Prodrugs
PubMed: 24594478
DOI: 10.1016/j.neuropharm.2014.02.014 -
PloS One 2023Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks.
METHODS
Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy.
RESULTS
We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006).
CONCLUSION
The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences.
CLINICAL TRIAL REGISTRATION NUMBER
CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
Topics: Humans; Dextroamphetamine; Caffeine; Healthy Volunteers; Dopamine; Australia; Amphetamine; Double-Blind Method
PubMed: 37440493
DOI: 10.1371/journal.pone.0287538