Dopamine-depleting agents

Symptomatic treatment. The chorea of Huntington s disease responds (partially) to treatment with neuroleptics, which, through blockade of D2 receptors, may help to increase basal ganglia output to more normal levels. Dopamine-depleting agents, such as reserpine or tetra-benazine have also been used. At best, these agents are only moderately effective and they should only be used if the chorea truly interferes with activities of daily living or produces social embarrassment. Neuroleptics and... 

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. 

As in AD, knowdedge of the neurotransmitter deficiency underlying PD, in this case dopamine, has been the basis for the development of therapy. Early studies show ed that cerebral dopamine was concentrated in the shiatum and that levodopa, the precursor to dopamine, could reverse the akinetic effects of the dopamine-depleting agent reserpine in experimental animals (Carlsson et al., 1957, 1958). Eventually, the identification of shiatal dopamine depletion as a key neurochemical finding in parkinsonian brains lead to heatment wdth levodopa in humans and to the subsequent advent of compounds that mimic the effects of dopamine or prolong its action (Table 39.2). 

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

In summary, treatments for tardive dyskinesia include cessation of the neuroleptic switching to a novel agent cholinergic agents and dopamine depleting drugs, such as reserpine or tetrabenazine. 

An increased incidence of depression in Parkinson s disease, as well as in patients receiving dopamine-depleting or antagonistic agents... 

The answers are 321-cT 322-e, 323-i. (Hardman, pp 238-239, 791.) Reserpine is an adrenergic neuronal blocking agent that causes depletion of central and peripheral stores of NE and dopamine Reserpine acts by irreversibly inhibiting the magnesium-dependent ATP transport process that functions as a carrier for biogenic amines from the cytoplasm... 

Involvement of endogenous 5-HT in emesis was investigated. It was found that reserpine, p-chlorophenylalanine (PCPA) and fenfluramine antagonized cisplatin-induced emesis in the ferret [109]. The real role of 5-HT was difficult to assess, as all these agents with a possible exception of PCPA, depleted 5-HT, dopamine (DA) and noradrenaline (NE), unselectively. Cisplatin, the potent emetogenic agent, moderately increased brain levels of DA and decreased NE, while it had no significant effect on 5-HT or 5-hydroxyindoleacetic acid. 

Dopamine antagonist activity is the hallmark of classical neuroleptics. The antihypertensive agents, reserpine (obsolete) and a-methyldopa, deplete neuronal stores of the amine. A common adverse effect of dopamine antagonists or depletors is parkinsonism. 

There is good evidence that propofol exerts an anti-emetic effect. The mechanism of this is unclear, but animal studies have shown that it may involve depleting the area postrema of serotonin as well as direct GABA-mediated inhibition, or inhibition of dopamine release in the brain. This probably requires a plasma concentration of over 350 ng-mL-1, and therefore will be seen when propofol is used as an induction agent for very short cases, or when it is used as an infusion in longer cases. Nitrous oxide... 

The exact mechanism of this peripheral adrenergic neuron blocking agent is not well defined. Reserpine administration results in depleted stores of norepinephrine, dopamine, and serotonin in multiple organs. The decreased peripheral resistance and cardiac output that results is manifested as a decrease in blood pressure. A central nervous system (CNS) effect may also play a role in decreasing blood... 

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. 

---