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Neuroscience and Biobehavioral Reviews 1992This article is a review of studies conducted on the effects of amphetamine on behavior in animals by the late Walter Isaac and his associates. The principle findings... (Review)
Review
This article is a review of studies conducted on the effects of amphetamine on behavior in animals by the late Walter Isaac and his associates. The principle findings and hypotheses developed over the 20 or more years of research are outlined and discussed. d-Amphetamine is thought to affect an organism's behavior by influencing the arousal level, mainly via the visual system.
Topics: Animals; Arousal; Dextroamphetamine; Humans
PubMed: 1480344
DOI: 10.1016/s0149-7634(05)80189-7 -
JAMA Psychiatry Feb 2018
Topics: Amphetamine; Cohort Studies; Dextroamphetamine; Methylphenidate; Pregnancy
PubMed: 29238801
DOI: 10.1001/jamapsychiatry.2017.3882 -
Psychopharmacology Jan 2001Because of the amphetamines' abuse potential and capability of exacerbating or inducing mood and psychotic disturbances, investigations of the behavioral effects of... (Review)
Review
BACKGROUND
Because of the amphetamines' abuse potential and capability of exacerbating or inducing mood and psychotic disturbances, investigations of the behavioral effects of amphetamines commonly involve non-human animals, with the laboratory rat being by far the most common species used. Although investigators of the behavioral effects of amphetamine in rats sometimes refer to doses used as being "low", "moderate", "high", etc., it is not clear in what sense these terms apply.
OBJECTIVES
To develop an operational definition of a low dose of amphetamine in rats, we reviewed studies that assessed the behavioral effects of dextroamphetamine (d-AMP) in rats in which some subset of doses, administered SC, IM or IP, was described as being "low". We then used the results of these studies to establish what the lowest effective dose ranges were across a variety of behavioral domains and compared these doses and their effects with those obtained with normal, healthy adult humans.
RESULTS
While the range of the lowest doses used in the studies with rats was quite broad (0.025-2.0 mg/kg), the median lowest effective doses observed (in the studies using doses of 0.125 mg/kg or less) were between 0.125 and 0.165 mg/kg across the behavioral domains of consummatory behavior, unconditioned or spontaneous behavior, learned behavior, and drug discriminative control. This range of doses was also found to be comparable to the lowest behaviorally effective doses of d-AMP (SC or PO) in normal human adults, which suggests that the sensitivity to the behavioral effects of amphetamine in these two species is fairly comparable.
CONCLUSIONS
Because of their ability to alter a wide variety of behaviors in rats, we conclude that low doses of d-AMP are in the 0.1-0.4 mg/kg range. Doses within this range typically: 1) constitute the ED50 in most drug discrimination/generalization procedures; 2) increase a variety of consummatory behaviors; 3) increase a variety of unconditioned or spontaneous motor activities; 4) increase low rate schedule-controlled behavior while exerting variable effects on high rate schedule controlled behavior; and 5) improve performance on some choice tasks, particularly those requiring sustained attention. Our analyses also indicate that, with respect to behavior, investigators do not always agree on what constitutes a low dose of amphetamine in rats and that doses assumed to be low for this species often are relatively high.
Topics: Animals; Behavior, Animal; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Rats
PubMed: 11205415
DOI: 10.1007/s002130000580 -
Paediatric Drugs 2007Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the... (Review)
Review
Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the US for the treatment of attention-deficit hyperactivity disorder in children aged 6-12 years. Lisdexamfetamine is a therapeutically inactive molecule. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the activity of the drug. In a well designed pharmacodynamic study in adult stimulant abusers, 50 or 100 mg doses of oral lisdexamfetamine had less likability than d-amphetamine 40 mg, suggesting a reduced abuse potential. Through rate-limited hydrolysis in the body, l-lysine is cleaved, gradually releasing pharmacologically active d-amphetamine. The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse. In two well designed trials in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD), the efficacy of lisdexamfetamine was superior to that of placebo in improving symptoms associated with ADHD. Adverse events with lisdexamfetamine were, in general, mild to moderate in severity and consistent with those commonly reported with amphetamine.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate
PubMed: 17407369
DOI: 10.2165/00148581-200709020-00007 -
The British Journal of Psychiatry : the... Jun 1981Dextroamphetamine (0.15 mg/kg) intravenously administered to a group of normal postmenopausal women induced a dysphoric reaction with drowsiness, annoyance, sadness and...
Dextroamphetamine (0.15 mg/kg) intravenously administered to a group of normal postmenopausal women induced a dysphoric reaction with drowsiness, annoyance, sadness and anger. Young normal men, receiving the same dosage, responded with elation of mood and alertness. It is suggested that age and hypoestrogenism may alter the behavioural response to amphetamine.
Topics: Adult; Affective Symptoms; Age Factors; Dextroamphetamine; Female; Humans; Injections, Intravenous; Male; Menopause; Middle Aged
PubMed: 7296174
DOI: 10.1192/bjp.138.6.470 -
Psychopharmacology Bulletin Jul 1975
Topics: Amphetamines; Animals; Brain; Dextroamphetamine; Drug Tolerance; Mice; Rats
PubMed: 1173942
DOI: No ID Found -
Journal of the American Veterinary... Mar 1976Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by...
Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by excitement, agitation, hyperthermia, and convulsive episodes that could be confused with other convulsant poisonings. Extraction procedures on stomach contents or urine enabled indentification of the drug, using ultraviolet spectrophotometry.
Topics: Acepromazine; Amphetamine; Animals; Body Temperature; Dextroamphetamine; Dog Diseases; Dogs; Female; Male; Pentobarbital; Seizures
PubMed: 1254519
DOI: No ID Found -
Journal of Veterinary Emergency and... 2024To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis.
OBJECTIVE
To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis.
CASE SUMMARY
A 3-year-old female neutered mixed breed dog initially presented with neurological signs suspected to be secondary to LDX toxicosis. The dog was treated as typical for amphetamine toxicoses but developed severe respiratory and cardiovascular signs throughout their hospitalization. The progression of the cardiopulmonary signs led to cardiopulmonary arrest, for which CPR was unsuccessful. Postmortem examination exhibited severe hemorrhage throughout multiple organ systems. Toxicology testing confirmed the presence of unaltered LDX and its metabolite, amphetamine.
NEW OR UNIQUE INFORMATION PROVIDED
This is the first case report documenting a severe progression of clinical signs and postmortem examination findings in a case of confirmed LDX toxicosis in a dog. Although the patient did not survive treatment, postmortem examination and microscopic evaluation of tissues allowed visualization of the extent of systemic pathophysiology. With prompt treatment, the prognosis of amphetamine toxicosis in dogs is generally considered good; however, this case report demonstrates a severe case in which even prompt and appropriate treatment did not prevent mortality. This suggests a need to establish negative prognostic indicators for which to monitor in cases of amphetamine toxicosis. Finally, this report is also unique in the fact that the LDX toxicosis was confirmed using a toxicological analysis technique not previously described clinically in dogs.
Topics: Humans; Female; Dogs; Animals; Lisdexamfetamine Dimesylate; Central Nervous System Stimulants; Dextroamphetamine; Attention Deficit Disorder with Hyperactivity; Treatment Outcome
PubMed: 38412018
DOI: 10.1111/vec.13370 -
Pharmacology, Biochemistry, and Behavior 1975In two-lever operant chambers, rats were trained in a food-reinforced discrimination task. Reward was contingent upon correct lever choices to the induced differential...
In two-lever operant chambers, rats were trained in a food-reinforced discrimination task. Reward was contingent upon correct lever choices to the induced differential cue conditions of d-amphetamine (0.8 mg/kg) or saline throughout training on a differential reinforcement of low response rate (DRL-15 sec) schedule. Upon acquisition of discriminative response control the animals were pretreated with various neurochemical agents. Pretreatment with atropine, phentolamine, propranolol, methysergide or cinanserin did not block production of d-amphetamine lever responding. Nicotine and oxotremorine did not produce the amphetamine-like cueing effect. However, pimozide blocked the ability of animals to discriminate d-amphetamine and L-DOPA, in combination with Ro 4-4602 with or without amantadine, generated amphetamine-like responses. These results indicate a role of dopamine in the production of the amphetamine state and from the failure of apomorphine to exhibit the stimulus property of d-amphetamine and the antagonism by alpha-methyltyrosine of the d-amphetamine responding it is further suggested that this amphetamine state is produced via the releasing of newly synthesized dopamine.
Topics: Animals; Dextroamphetamine; Discrimination, Psychological; Dopamine; Drug Interactions; Extinction, Psychological; Male; Rats; Receptors, Drug; Reinforcement Schedule; Time Factors
PubMed: 1223898
DOI: 10.1016/0091-3057(75)90021-0 -
Clinical Pharmacology and Therapeutics Dec 1994l-Deprenyl has dose-dependent amphetamine- and methamphetamine-like discriminative stimulus properties in rats and monkeys. However, these actions occur only at doses...
l-Deprenyl has dose-dependent amphetamine- and methamphetamine-like discriminative stimulus properties in rats and monkeys. However, these actions occur only at doses that are well above the clinically relevant dose range for l-deprenyl and are likely to reflect its metabolic conversion to amphetamine products. In view of its weak potency for producing amphetamine-like effects and their slow onset, it may not be surprising that l-deprenyl does not appear to have amphetamine-like abuse potential and has been used therapeutically in the treatment of Parkinson syndrome for more than 20 years with no reported instances of abuse.
Topics: Amphetamine; Amphetamines; Animals; Dextroamphetamine; Discrimination Learning; Dose-Response Relationship, Drug; Rats; Saimiri; Selegiline
PubMed: 7995019
DOI: 10.1038/clpt.1994.207