Early pharmacokinetics and clinical effects of oral d-amphetamine in normal subjects

Angrist, Burt; Corwin, June; Bartlik, Barbara; Cooper, Thomas B.

doi:10.1016/0006-3223(87)90070-9

Cited by 165 publications

(98 citation statements)

References 25 publications

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“…The behavioral effects of d-amphetamine peaked at approximately two hours following administration, in agreement with previous human laboratory research (e.g., Chait et al, 1985;Kelly et al, 1993;Rush et al, 1998) and the time course for peak plasma levels following oral administration (Angrist et al, 1987). Thus, the peak effects of the damphetamine pretreatment dose occurred during completion of the modified progressive-ratio procedure in Self-Administration Sessions.…”

Section: Discussionsupporting

confidence: 88%

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans

Stoops¹,

Vansickel²,

Lile³

et al. 2007

Pharmacology Biochemistry and Behavior

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Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaineusing individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified-progressive ratio procedure in two sessions in which they received pretreatments with either 0 or 15 mg oral d-amphetamine 2 hours prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressiveratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

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Section: Discussionsupporting

confidence: 88%

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans

Stoops¹,

Vansickel²,

Lile³

et al. 2007

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

show abstract

“…rather than i.v. Oral drug administration is associated with lower and more variable bioavailability (Angrist et al, 1987;Ylitalo, 1991). Nonetheless, plasma levels of amphetamine did not differ on the two test sessions, and we have previously shown that the dose used here induces significant decreases in [ 11 C]raclopride BP in ventral striatum .…”

Section: Discussionmentioning

confidence: 56%

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Leyton

Dagher

Boileau

et al. 2003

Neuropsychopharmacol

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Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [ 11 C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [ 11 C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [ 11 C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t ¼ 4.2, equivalent to po0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [ 11 C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t ¼ 6.31; x ¼ À25, y ¼ À8, and z ¼ 0.1). In the t-map defined cluster, [ 11 C]raclopride BP values were 11.8 7 11.9% higher during the APTD session (po0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r ¼ À0.82, po0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.

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“…For example, amphetamine is known to have vasoconstrictive effects, which can result in alterations of blood flow (Simpson 1976;Angrist et al 1987;Brauer et al 1996). Although it seems unlikely, amphetamine may have directly affected blood flow only in the specific brain areas where changes in the activation pattern were observed.…”

Section: Discussionmentioning

confidence: 99%

An fMRI Study of the Effect of Amphetamine on Brain Activity,

Uftring

Wachtel

Chu

et al. 2001

Neuropsychopharmacology

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Early pharmacokinetics and clinical effects of oral d-amphetamine in normal subjects

Cited by 165 publications

References 25 publications

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans

Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

An fMRI Study of the Effect of Amphetamine on Brain Activity,

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