Dopamine transporter availability in medication free and in bupropion treated depression: A 99mTc-TRODAT-1 SPECT study

Árgyelán, Miklós; Szabó, Zoltán; Kanyó, Balázs; Tanács, Attila; Kovács, Zsuzsanna; Janka, Zoltán; Pajor, László

doi:10.1016/j.jad.2005.08.016

Cited by 89 publications

(51 citation statements)

References 20 publications

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“…Importantly, our predictions of the much larger exposure to the metabolite in brain ECF agree with its reported 7-fold higher concentrations than bupropion in human CSF (Cooper, et al, 1994). Receptor occupancy studies using PET (Meyer et al, 2002;LearnedCoughlin et al, 2003) or SPECT (Argyelán et al, 2005) tracers specific for DAT, and after attainment of steady-state kinetics based on several days of dosing 150 mg of the SR formulation twice daily, indicate modest occupancy of around 20% in both patients with and without depression. In one of these studies (Learned-Coughlin et al, 2003), DAT occupancy was sustained for at least 24 hours.…”

Section: Bupropion and Hydroxybupropion Brain Pharmacokinetics 629supporting

confidence: 79%

Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations

Cremers

Flik

Folgering

et al. 2016

Drug Metabolism and Disposition

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Administration of bupropion [(6)-2-(tert-butylamino)-1-(3-chlorophenyl) propan-1-one] and its preformed active metabolite, hydroxybupropion [(6)-1-(3-chlorophenyl)-2-[(1-hydroxy-2-methyl-2-propanyl)amino]-1-propanone], to rats with measurement of unbound concentrations by quantitative microdialysis sampling of plasma and brain extracellular fluid was used to develop a compartmental pharmacokinetics model to describe the blood-brain barrier transport of both substances. The population model revealed rapid equilibration of both entities across the blood-brain barrier, with resultant steadystate brain extracellular fluid/plasma unbound concentration ratio estimates of 1.9 and 1.7 for bupropion and hydroxybupropion, respectively, which is thus indicative of a net uptake asymmetry. An overshoot of the brain extracellular fluid/plasma unbound concentration ratio at early time points was observed with bupropion; this was modeled as a time-dependent uptake clearance of the drug across the blood-brain barrier. Translation of the model was used to predict bupropion and hydroxybupropion exposure in human brain extracellular fluid after twice-daily administration of 150 mg bupropion. Predicted concentrations indicate that preferential inhibition of the dopamine and norepinephrine transporters by the metabolite, with little to no contribution by bupropion, would be expected at this therapeutic dose. Therefore, these results extend nuclear imaging studies on dopamine transporter occupancy and suggest that inhibition of both transporters contributes significantly to bupropion's therapeutic efficacy.

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Section: Bupropion and Hydroxybupropion Brain Pharmacokinetics 629supporting

confidence: 79%

Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations

Cremers

Flik

Folgering

et al. 2016

Drug Metabolism and Disposition

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“…It is a weak dopamine (DA) reuptake blocker. Indeed, several studies demonstrated that clinically effective doses of bupropion induce an occupancy of DA transporters in the 15% range (Meyer et al 2002;Kugaya et al 2003;Learned-Coughlin et al 2003;Argyelan et al 2005). Such a weak blockade action of bupropion at DA transporters in humans is consistent with the lack of effect of bupropion on the firing rate of ventral tegmental area DA neurons after both 2 and 14 days (Dong and Blier 2001;El Mansari et al 2008).…”

Section: Introductionmentioning

confidence: 76%

Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion

2011

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“…Yet, while preclinical studies have shown that treatment with the reuptake blockers methylphenidate and bupropion reversed MAinduced reductions in VMAT-2 activity, bupropion did not prevent the long-term deficits in dopaminergic function produced by repeated high-dose MA administration (Rau et al, 2005;Sandoval et al, 2003), which may explain the lack of clinical effect for bupropion among heavy-MA users. Alternatively, bupropion's relatively weak effect in blocking DA reuptake (Argyelan et al, 2005;Meyer et al, 2002) may simply be overwhelmed by chronic highdose MA use.…”

Section: Discussionmentioning

confidence: 99%

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Shoptaw

Heinzerling

Rotheram-Fuller

et al. 2008

Drug and Alcohol Dependence

138

129

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Objective-To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants.Methods-Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions.Results-There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR=2.81, 95% CI=1.61-4.93, p<0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost 5 cigarettes per day (p=0.0002).Conclusion-Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light MA users is warranted.

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Dopamine transporter availability in medication free and in bupropion treated depression: A 99mTc-TRODAT-1 SPECT study

Cited by 89 publications

References 20 publications

Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations

Development of a Rat Plasma and Brain Extracellular Fluid Pharmacokinetic Model for Bupropion and Hydroxybupropion Based on Microdialysis Sampling, and Application to Predict Human Brain Concentrations

Enhancement of serotonergic and noradrenergic neurotransmission in the rat hippocampus by sustained administration of bupropion

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

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