Dopamine transporter agents

Radiopharmaceutical dopamine transport,., , agents. (VI). having a selective... 

Hsin, L.-W., Dersch, C.M., Baumann, M.H. et al. (2002) Development of long-acting dopamine transporter ligands as potential cocaine-abuse therapeutic agents chiral hydroxyl-containing derivatives of l-[2-[bis (4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine and l-[2-(diphenylmethoxy)ethyl]-4-(3-phe-nylpropyl)piperazine. Journal of Medicinal Chemistry, 45 (6), 1321-1329. 

Dopamine depleting agents. Reserpine, a natural alkaloid that blocks vesicular transport of monoamines, depletes stored monoamines, including DA. DA depletion is associated with the emergence of parkinsonism. This effect of reserpine was among the first clues that PD is the result of DA deficiency (see above). Generally, the parkinsonism resulting from reserpine is reversible. 

Meltzer, P. C.,Blundell, P., Jones,A. G. etal. A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain. J. Med. Chem. 40 1835-1844, 1997. 

Altropane and ioflupane bind L-dopamine transporter protein. They are being developed, respectively, as potential contrast agent for radioimaging and imaging... 

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... 

The affinities and transporter selectivities of experimental agents were assessed in brain tissue of adult cynomolgus or rhesus monkeys (Macaca fasicularis or Macaca mulatto). Caudate-putamen was the source of the dopamine and serotonin transporters. The dopamine transporter affinity was measured with [3H]WIN 35428 ([3H]CFT), while the serotonin transporter was measured with [3H]citalopram. Testing data are provided in Table 2. 

Table 2 Binding affinities data of selected experimental agents as inhibitors of [3H]WIN 35428 binding to the dopamine transporter and [3H]citalopram binding to the serotonin transporter in adult cynomolgus or rhesus monkeys...

The dopamine uptake system - or dopamine transporter system - is inhibited by the following clinically used agents amfonelic acid, bupropion, mazindot or experimental agents, nomifensine, indatraline, p-CFT, p-ClT-FP, GYKl 52895 and LR 5182. 

Figure 12.11. Radioligands for dopamine neurons. The se include [ F] -labeled dopa and nonhydro-lyzable, long-acting phenyltropane analogs of cocaine, which bind selectively to the dopamine transporter proteins and are highly specific markers of dopamine neurpns. These agents are useful for imaging with C F] for PET and for SPECT.

Cocaine inhibits the transporters for norepinephrine, serotonin, and dopamine. Binding of cocaine to the dopamine transporter Inhibits reuptake of dopamine, thus prolonging signaling at key brain synapses indeed, the dopamine transporter Is the principal brain cocaine receptor. Therapeutic agents such as the antidepressant drugs fluoxetine (Prozac) and imipramlne block serotonin uptake, and the tricyclic antidepressant desipramine blocks norepinephrine uptake. I... 

Recently, the development of " Tc-labcled tropane derivatives used as dopamine transporter imaging agents has been reported. The dopamine transporter is a protein complex located prcsynaptically at dopaminergic nerve terminals [247]. It is depleted in Parkinson s disease, and the extent of depletion correlates with the loss of dopamine [248], Among a series of tropane derivatives [249,250] labeled with " Tc, two compounds deserve more attention. 

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