n-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane and Attention-Deficit-Disorder-with-Hyperactivity

There is converging evidence of the role of catecholamine dysregulation in the underlying pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent genetic, treatment, and imaging studies have highlighted the role of DAT in ADHD. There is an emerging literature on in vivo neuroreceptor imaging of DAT in ADHD and control subjects reported by a number of groups internationally. A comprehensive review of existing imaging studies of DAT binding in ADHD shows that six of eight independent studies by six different groups have reported increased DAT binding in (mostly) treatment-naïve children and adults with ADHD. Although there is fair agreement regarding the presence and direction of abnormal DAT binding, there remains disagreement as to the magnitude of the finding and the importance of many potentially confounding variables, including clinical characteristics and imaging methodology. Three studies by three different groups have reported decreased DAT binding after methylphenidate treatment. Interpretation of the latter finding awaits clarification of the issue of timing of drug administration and imaging to disentangle receptor occupancy from downregulation.

Topics: Age Factors; Animals; Attention Deficit Disorder with Hyperactivity; Brain Mapping; Carbon Isotopes; Cocaine; Dopamine Plasma Membrane Transport Proteins; Humans; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Sensory Receptor Cells; Time Factors; Tomography, Emission-Computed

Boston Life Sciences (BLS) is developing Altropane as a potential radio-imaging agent to be used with single photon emission tomography (SPECT), for the early diagnosis of Parkinson's disease (PD) and attention deficit hyperactivity disorder (ADHD) [329661]. Altropane is currently in phase III clinical trials for PD and phase II clinical trials for ADHD.

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Clinical Trials as Topic; Cocaine; Humans; Parkinson Disease; Radiopharmaceuticals; Technology, Pharmaceutical; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The main aim of this study was to examine the relationship between dopamine transporter (DAT) binding in the striatum in individuals with and without attention-deficit/hyperactivity disorder (ADHD), attending to the 3'-untranslated region of the gene (3'-UTR) and intron8 variable number of tandem repeats (VNTR) polymorphisms of the DAT (SLC6A3) gene.. Subjects consisted of 68 psychotropic (including stimulant)-naïve and smoking-naïve volunteers between 18 and 55 years of age (ADHD n = 34; control subjects n = 34). Striatal DAT binding was measured with positron emission tomography with 11C altropane. Genotyping of the two DAT (SLC6A3) 3'-UTR and intron8 VNTRs used standard protocols.. The gene frequencies of each of the gene polymorphisms assessed did not differ between the ADHD and control groups. The ADHD status (t = 2.99; p<.004) and 3'-UTR of SLC6A3 9 repeat carrier status (t = 2.74; p<.008) were independently and additively associated with increased DAT binding in the caudate. The ADHD status was associated with increased striatal (caudate) DAT binding regardless of 3'-UTR genotype, and 3'-UTR genotype was associated with increased striatal (caudate) DAT binding regardless of ADHD status. In contrast, there were no significant associations between polymorphisms of DAT intron8 or the 3'-UTR-intron8 haplotype with DAT binding.. The 3'-UTR but not intron8 VNTR genotypes were associated with increased DAT binding in both ADHD patients and healthy control subjects. Both ADHD status and the 3'-UTR polymorphism status had an additive effect on DAT binding. Our findings suggest that an ADHD risk polymorphism (3'-UTR) of SLC6A3 has functional consequences on central nervous system DAT binding in humans.

Topics: 3' Untranslated Regions; Adolescent; Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Cocaine; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Genomics; Humans; Male; Middle Aged; Minisatellite Repeats; Polymorphism, Genetic; Radionuclide Imaging; Risk Factors; Young Adult

The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however.. Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-naïve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD.. Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder.. These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Chi-Square Distribution; Cocaine; Corpus Striatum; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Middle Aged; Positron-Emission Tomography

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Biological Psychiatry; Child; Cocaine; Gamma Cameras; Humans; Radiopharmaceuticals; Receptors, Dopamine