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Although inhibition of dopamine transporters (DAT) and the subsequent increase in dopamine clearly play a role in the effects of psychomotor stimulants, the reinforcing effectiveness of DAT inhibitors varies. Previous studies suggest that pharmacokinetic and pharmacodynamic properties of these drugs account for this variability. The present studies compared(More)
Reboxetine analogues with methyl and fluoroalkyl substituents at position 2 of the phenoxy ring 1-4 were synthesized. In vitro competition binding with [(3)H]nisoxetine demonstrated that 1-4 have a high affinity for the norepinephrine transporter (NET) with K(i)'s = 1.02, 3.14, 3.68, and 0.30 nM, respectively. MicroPET imaging in rhesus monkeys showed that(More)
INTRODUCTION In vivo imaging of the serotonin transporter continues to be a valuable tool in drug development and in monitoring diseases that alter serotonergic function. The purposes of this study were to: 1) evaluate the test/retest reproducibility of [¹²³I] 2β-Carbomethoxy-3β-(3'-((Z)-2-iodoethenyl)phenyl)nortropane ([¹²³I]mZIENT); and 2) to assess(More)
The positron emission tomography (PET) tracer 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane ((18)F-FECNT) is a highly specific ligand for dopamine transporter (DAT) that yields higher peak striatum-to-cerebellum ratios and offers more favorable kinetics than most (18)F-radiolabeled DAT ligands currently available. The goal of this(More)
Acute SSRI (selective serotonin reuptake inhibitor) treatment has been shown to attenuate the abuse-related effects of cocaine; however, SSRIs have had limited success in clinical trials for cocaine abuse, possibly due to neurobiological changes that occur during chronic administration. In order to better understand the role of serotonin (5HT) in cocaine(More)
BACKGROUND Deficits in serotonergic neurotransmission have been implicated in the pathogenesis of depression and suicidality. The present study utilized a novel positron-emission tomography (PET) ligand to quantitate and compare brain regional serotonin transporter (SERT) binding potential in depressed patients with a past history of suicide attempts to(More)
The meta-vinylhalide fluoroalkyl ester nortropanes 1-4 were synthesized as ligands of the serotonin transporter (SERT) for use as positron emission tomography (PET) imaging agents. In vitro competition binding assays demonstrated that 1-4 have a high affinity for the SERT (K(i) values = 0.3-0.4 nM) and are selective for the SERT over the dopamine and(More)
The goal of the present study was to examine how social subordination stress and 5HTT polymorphisms affect the development of brain serotonin (5HT) systems during the pubertal transition in female rhesus monkeys. We also examined associations with developmental changes in emotional reactivity in response to a standardized behavioral test, the Human Intruder(More)
A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K(M) of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the(More)
A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (⩽1.2 nM) to the CRF1 receptor when(More)