Comparative studies of various amphetamine analogues demonstrating different interactions with the metabolism of the catecholamines in the brain

Scheel-Krüger, Jørgen

doi:10.1016/0014-2999(71)90121-x

Cited by 381 publications

(70 citation statements)

References 25 publications

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“…This extends previous findings that another dopamine-releasing agent, methamphetamine, redistributes VMAT-2 similarly. Importantly, this study demonstrates that amphetamine-induced trafficking occurs at 2 mg/kg, a dose that causes hyperlocomotive behavior (Scheel-Kruger, 1971), and is presumed clinically relevant (Schiffer et al, 2006). In contrast to amphetamine, results confirm a previous study that methylphenidate redistributes vesicles from the plasmalemmal membrane-associated to the cytoplasmic, non-membraneassociated fraction.…”

Section: Discussionsupporting

confidence: 84%

Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2

Riddle

Hanson

Fleckenstein

2007

European Journal of Pharmacology

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High-dose administration of psychostimulants traffics the vesicular monoamine transporter-2 (VMAT-2), as assessed by subcellular fractionation of rat striatal tissue. This study demonstrates that administration of low doses of amphetamine or methylphenidate differentially traffic VMAT-2 within nerve terminals, with effects similar to those observed after high-dose administration. Trafficking of vesicular glutamate, acetylcholine, or GABA transporters was not altered by high-or low-dose amphetamine or methylphenidate treatment. These data represent the first report that amphetamine redistributes VMAT-2 protein. In addition, these data demonstrate that the trafficking of VMAT-2 after amphetamine or methylphenidate is selective for monoaminergic neurons.

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Section: Discussionsupporting

confidence: 84%

Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2

Riddle

Hanson

Fleckenstein

2007

European Journal of Pharmacology

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“…A landmark study by Brozoski et al [91] demonstrated that 6-hydroxydopamine lesions of the dorsolateral prefrontal cortex in rhesus monkeys was as devastating to memory performance as removing the cortex itself, and that, importantly, this impaired performance could be reversed by DA agonists such as L-dopa and apomorphine. In relation to this, it is useful to note that Elliott et al [92] have demonstrated significantly enhanced performance in tests of spatial working memory and planning in healthy young adults, using methylphenidate, a stimulant related to amphetamine [93]. It is therefore clear that much can be accrued from a comparative approach to frontal lobe function not only for our understanding of the neuropsychological deficits in patients with fvFTD, but also for the development of successful therapeutic strategies.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Comparative Cognitive Neuropsychological Studies of Frontal Lobe Function: Implications for Therapeutic Strategies in Frontal Variant Frontotemporal Dementia

Rahman

Robbins

Sahakian³

1999

Dement Geriatr Cogn Disord

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Patients with mild frontal variant frontotemporal dementia (fvFTD) who attend the clinic are usually unaware of the pervasive changes in their personality and behaviour, despite the fact it is these changes which have prompted the referral from the patient’s spouse or carer. Comparative studies across various species offer unique insights into the heterogeneous structure and functions of the prefrontal cortex, and can allow a novel approach to the precise identification of the neuropsychological deficits present in these patients. We have found that they may show marked deficits on tests sensitive to ventromedial prefrontal or orbitofrontal function, in the relative absence of impairments on tests sensitive to dorsolateral prefrontal function. We highlight important differences in the neurocognitive profile of these patients with that of patients with other neurodegenerative conditions, including basal ganglia diseases and dementia of the Alzheimer type. The specific nature of these neuropsychological deficits, together with converging evidence from clinical and neuropathological studies, may provide useful clues about the predominant locus of dysfunction in the early stages of fvFTD and possible underlying neurotransmitter abnormalities. This is important for the successful development of therapeutic intervention strategies for both cognitive and behavioural symptoms in fvFTD. Finally, we evaluate critically the rationales for therapeutic modulation of noradrenergic, serotonergic and dopaminergic neurotransmitter systems at various stages of disease.

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“…Amphetamine, a sympathomimetic agent, acts on the central nervous system to affect locomotor activity (6)(7)(8)(9), appetite (10), and thermoregulation (11)(12)(13)(14); in high doses, it causes a psychotic reaction in humans that resembles paranoid schizophrenia (15). Catecholamine-containing brain neurons appear to mediate many of the behavioral and physiological effects of this drug (16).…”

mentioning

confidence: 99%

D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.

Moskowitz¹,

Weiss²,

Lytle³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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Brain polysomes are disaggregated in rats given moderate to large doses of d-amphetamine sulfate; this response is rapid in onset, lasts for at least 4-6 hr, and varies with the age of the animal. Pretreatment with a dopamine receptor blocking agent, haloperidol or pimozide, blocks the amphetamine-induced disaggregation.Rats treated with large single doses of i-dopa (a catecholamine precursor) exhibit a major disaggregation of brain polysomes (1) and a parallel decrease in the net rate of brain protein synthesis (2, 3). The L-dopa-induced disaggregation of brain polysomes is suppressed in animals pretreated with drugs that block the conversion of dopa to dopamine, or with drugs that block dopamine receptors (4, 5). Hence, the drug-induced polysome disaggregation may result from a direct action of dopamine on a receptor that controls the intracellular proteinsynthetic apparatus.Amphetamine, a sympathomimetic agent, acts on the central nervous system to affect locomotor activity (6-9), appetite (10), and thermoregulation (11-14); in high doses, it causes a psychotic reaction in humans that resembles paranoid schizophrenia (15). Catecholamine-containing brain neurons appear to mediate many of the behavioral and physiological effects of this drug (16). Relatively little information exists regarding effects of amphetamine on brain protein synthesis. We now report that large doses of d-amphetamine sulfate disaggregate brain polysomes in rats, and that this effect, like that of -dopa, appears to be mediated by dopamine receptors. MATERIALS AND METHODSMale albino rats of various ages (Charles River Laboratories, Wilmington, Mass.) were exposed to light from 9 a.m. to 9 p.m. and given free access to food and water. All animals were maintained at ambient temperatures ranging from 20-22'. Animals less than 26 days of age remained with the dam in litters of eight pups; older animals were caged in groups of four for 1 day prior to an experiment. All injections were administered intraperitoneally.Polysomes were prepared as described (1, 4). Briefly, the brains were removed, pooled two per sample, minced, and homogenized in an ice-cold 0.25 M sucrose medium containing 0.05 M Tris, HCl, 0.10 M KCl, and 0.012 M MgCl2, at pH 7.6. The homogenates were then centrifuged for 20 min at 21,000 X g; the post-mitochondrial supernatants were treated with sodium deoxycholate to a concentration of 1% and then layered over discontinuous sucrose gradients (0.5 M, 2.0 M). After this centrifugation, the pellets of ribosomes were again suspended and applied to a 10-40% continuous sucrose gradient. Absorbance profiles were recorded at 260 nm. The percentage of polysomes in the profile represents the fraction of total area attributable to polyribosomes (1, 4, 5). RESULTSIn the first experiment, 26-day-old animals received 0.9% (w/v) saline vehicle (1 ml/kg) or d-amphetamine sulfate (1.5, 10, 15, or 50 mg/kg, salt weight); they were decapitated 1 hr later. Doses of 10 mg/kg of d-amphetamine or larger disaggregated the brain polysomes; the m...

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Comparative studies of various amphetamine analogues demonstrating different interactions with the metabolism of the catecholamines in the brain

Cited by 381 publications

References 25 publications

Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2

Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2

Comparative Cognitive Neuropsychological Studies of Frontal Lobe Function: Implications for Therapeutic Strategies in Frontal Variant Frontotemporal Dementia

D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism.

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