Dopamine transporter disorders

Jaber M., Jones S., Giros B., Caron M. G. (1997). The dopamine transporter a crucial component regulating dopamine transmission. Mov. Disord. 12(5), 629-33. 

Dresel, S., Krause, J., Krause, K. H. et al. Attention deficit hyperactivity disorder binding of 99mTc TRODAT-1 to the dopamine transporter before and after methylphenidate treatment. Eur. J. Nucl. Med. 27 1518-1524,2000. 

Varrone, A., Marek, K. L., Jennings, D. et al. 123I 5-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson s disease and multiple system atrophy. Mov. Disord. 16 1023-1032, 2001. 

Monoamine reuptake inhibitors elevate extracellular levels of serotonin (5-HT), norepinephrine (NE) and/or dopamine (DA) in the brain by binding to one or more of the transporters responsible for reuptake, namely the serotonin transporter (SERT), the norepinephrine transporter (NET) and the dopamine transporter (DAT), thereby blocking the reuptake of the neurotransmitter(s) from the synaptic cleft [1], Monoamine reuptake inhibitors are an established drug class that has proven utility for the treatment of a number of CNS disorders, especially major depressive disorder (MDD). 

The dopamine transporter has been a target for developing pharmacotherapies for a number of CNS disorders including ADHD, stimulant abuse, depression and Parkinson s disease. Several excellent reviews in this area have been recently published [28-30]. The dopamine reuptake inhibitor methylphenidate has been successfully used for decades in the management of ADHD in children and adolescents. It remains a first-line treatment along with amphetamine for this disorder [31,32]. 

Vandenbergh, D. J., Thompson, M. D., Cook, E. H., et al. (2000) Human dopamine transporter gene coding region conservation among normal, Tourette s disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol. Psychiatry. 5, 283-292. 

Dopamine Transporter SLC6A3 Inhibitors will prevent dopamine uptake (cocaine-like drugs). Important effects on locomotor activity, motivation, reward and cognition, dopaminergic hyperactivity, ADHD, depression. Parkinsonism, psychotic disorders, seizure, dystonia, dyskinesia. 

Curran, S., Mill, J., Tahir, E., Kent, L., Richards, S., Gould, A., Huckett, L., Sharp, J., Batten, C., Fernando, S., Ozbay, F., Yaz-gan, Y., Simonoff, E., Thompson, M., Taylor, E., and Asherson, P. (2001) Association study of a dopamine transporter polymorphism and attention deficit hyperactivity disorder in UK and Turkish samples. Mol Psychiatry 6 425-428. 

Gill, M., Daly, G., Heron, S., Haw, Z., and Fitzgerald, M. (1997) Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry 2 311—313. 

Kelsoe, J., Sadovnick, A., Kristbjarnarson, H., Bergesch, P., Mroczkowski-Parker, Z., Drennan, M., Rapaport, M., Flodman, P., Spence, M., and Remick, R. (1996). Possible locus for bipolar disorder near the dopamine transporter on chromosome 5. Am J Med Genet (Neuropsychiatr Genet) 67 533-540. 

Waldman, I.D., Robinson, B.E, and Feigon, S.A. (1997) Linkage disequilibrium between the dopamine transporter gene (DATl) and bipolar disorder extending the transmission disequilibrium test (TDT) to examine genetic heterogeneity. Genet Epidemiol 14(6) 699-704. 

Waldman, I., Rowe, D., Abramowitz, A., Kozel, S., Mohr, J., Sherman, S., Cleveland, H., Sanders, M., Card, J., and Stever, C. (1998) Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet 63 1767-1776. 

Dougherty, D.D., Bonab, A.A., Spencer, T.J., Rauch, S.L., Madras, B.K., and Fischman, A.J. (1999) Dopamine transporter density is elevated in patients with attention deficit hyperactivity disorder. Lancet 354 2132-2133. 

Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder effects of methyl-... 

Cook, Edwin H., Mark A. Stein, Matthew D. Krasowski, Nancy J. Cox, Deborah M. Olken, John E. Kieffer, and Bennett L. Leventhal. 1995. "Association of Attention Deficit Disorder and the Dopamine Transporter Gene." American Journal of Human Generics 56 993-98. 

The most commonly used agents to enhance attention in attention deficit disorder are the stimulants methylphenidate and ( -amphetamine. Other effective stimulants are not as widely used, pemoline because of liver toxicity and methamphetamine because of its greater abuse potential. Methylphenidate and ( -amphetamine act predominantly by releasing dopamine from presynaptic dopamine terminals (Figs. 12— 2 and 12—3). These agents not only block the dopamine transporter but may actually... 

Uhl GR (2003) Dopamine transporter basic science and human variation of a key molecule for dopaminergic function, locomotion and Parkinsonism. Mov Disord 7S(Suppl. 7) S71-S80. 

Neumeister A, Willeit M, Praschak-Rieder N, Asenbaum S, Stastny J, Hilger E, Pirker W, Konstantinidis A, Kasper S (2001) Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls. Psychol Med 37 1467-1473. 

Tropane derivatives, (V), prepared by Kozikowski (5) were highly selective as dopamine transporters as well as for selectively inhibiting serotonin reuptake and/or norepinephrine and used in the treatment of psychiatric and neurodegenerative disorders. 

Keywords Dopamine transporter Norepinephrine transporter Serotonin transporter Polymorphism Attention deficit h5rperactivity disorder Parkinson s disease Addiction Anxiety Depression Autism... 

Chen CK, Chen SL, Mill J, Huang YS, Lin SK, Curran S, Purcell S, Sham P, Asherson P (2003) The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample. Mol Psychiatry 8 393-396... 

Cook EH, Leventhtil BL (1996) The serotonin system in autism. Curr Opin Pediatr 8 348-354 Cook EH Jr., Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL (1995) Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56 993-998... 

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