Abstract:
RATIONALE:Drugs that rapidly increase dopamine levels have an increased risk of abuse. Dasotraline (DAS) is a dopamine and norepinephrine reuptake inhibitor characterized by slow oral absorption with low potential for abuse. However, it remains unclear whether intravenous (i.v.) administration would facilitate the rapid elevation of dopamine levels associated with stimulant drugs. OBJECTIVE:To assess the kinetics of DAS across the blood-brain barrier and time to onset of dopamine transporters (DAT) inhibition. METHODS:We compared the onset of DAT occupancy and the associated elevation of synaptic dopamine levels in rhesus monkey following i.v. administration of DAS or methylphenidate (MPH) using positron emission tomography (PET). Brain entry times were estimated by reductions in [18F]-FE-PE2I binding to DAT in rhesus monkeys. Elevations of synaptic dopamine were estimated by reductions in [11C]-Raclopride binding to D2 receptors. RESULTS:Intravenous administration of DAS (0.1 and 0.2 mg/kg) resulted in striatal DAT occupancies of 54% and 68%, respectively; i.v. administered MPH (0.1 and 0.5 mg/kg) achieved occupancies of 69% and 88% respectively. Brain entry times of DAS (22 and 15 min, respectively) were longer than for MPH (3 and 2 min). Elevations in synaptic dopamine were similar for both DAS and MPH however the time for half-maximal displacement by MPH (t = 23 min) was 4-fold more rapid than for DAS (t = 88 min). CONCLUSIONS:These results demonstrate that the pharmacodynamics effects of DAS on DAT occupancy and synaptic dopamine levels are more gradual in onset than those of MPH even with i.v. administration that is favored by recreational drug abusers.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Lew R,Constantinescu CC,Holden D,Carson RE,Carroll V,Galluppi G,Koblan KS,Hopkins SCdoi
10.1007/s00213-020-05623-8subject
Has Abstractpub_date
2020-11-01 00:00:00pages
3435-3446issue
11eissn
0033-3158issn
1432-2072pii
10.1007/s00213-020-05623-8journal_volume
237pub_type
杂志文章abstract:RATIONALE:Increasing concomitant abuse of cocaine and morphine-like opioids has prompted a number of studies aimed at understanding how these drugs interact. OBJECTIVE:The present study was designed to determine if variations in opioid pretreatment time would affect how mu opioid agonists interact with cocaine. METHO...
journal_title:Psychopharmacology
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abstract::The effects of diazepam (10 mg orally) on the responding of normal human volunteers was studied in a procedure that involved the maintenance of operant behavior by monetary reinforcement and its suppression by monetary loss (punishment). Diazepam produced an antipunishment effect as shown by an increase in behavior su...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2016-10-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-10-01 00:00:00
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doi:10.1007/s00213-007-1063-x
更新日期:2008-04-01 00:00:00
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更新日期:1993-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::This study examined and compared withdrawal signs and symptoms from cessation of 0, 2 and 4 mg nicotine gum. In addition, a comparison was made between nicotine gum versus cigarette withdrawal symptoms. Smokers first underwent cigarette deprivation for 4 days and then were randomly assigned to 0 (N = 16), 2 (N = 25), ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-02-01 00:00:00
abstract::The tricyclic anticonvulsant carbamazepine (CBZ) is effective in pain and affective disorder, but the mechanism of action for this drug has not been defined. Recently it was reported that CBZ had interaction with adenosine receptor, which is related to the inhibition of release of neurotransmitter. In the present stud...
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更新日期:2006-09-01 00:00:00
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更新日期:2015-11-01 00:00:00
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更新日期:2016-12-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
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更新日期:1987-01-01 00:00:00
abstract:RATIONALE:It is important to study age-related differences that may put adolescents at risk for alcohol-related problems. Adolescents seem less sensitive to the aversive effects of ethanol than adults. Less is known of appetitive effects of ethanol and stress modulation of these effects. OBJECTIVES:This study aims to ...
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更新日期:2013-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2007-11-01 00:00:00