Neurotransmitters replacement

Since the detection of DA deficiency in PD, neurotransmitter replacement has been the therapy of choice (Coleman, 1992). The transmitter has been applied in form of its precursor L-DOPA, combined with a peripheral decarboxylase inhibitor (e.g. benserazide), so that the drug s efficacy develops only in the CNS. L-DOPA is stored in the remaining nigrostriatal dopaminergic neurons, de-carboxylated to DA and then released. It acts post-synaptically on D and D2 receptors, so that the natural function of the transmitter is imitated and the clinical signs improve. The patients reach a non-fluctuating, constant degree of mobility. 

One limitation of this method is that the specific activity of the radiolabel is progressively diluted as the radiolabelled transmitter is released from neurons and replaced by that derived from unlabelled substrate. This method also assumes that there is no compartmentalisation of the terminal stores, yet there is ample evidence that newly synthesised acetylcholine and monoamines are preferentially released. An alternative approach is to monitor the rate at which the store of neurotransmitter is depleted after inhibition of its synthesis (Fig. 4.1). However, the rate of release of some neurotransmitters (e.g. 5-HT) is partly governed by their rate of synthesis and blocking synthesis blunts release. 

Symptomatic detoxification from nicotine is achieved with any of the currently available nicotine replacement therapies (NRTs) or a combination thereof.25 Several CNS neurotransmitters... 

Replacement of a deficient neurotransmitter. Finally, synaptic activity may be altered by replacement of a deficient neurotransmitter, a form of... 

The answer is b. (Hardman, p 790.) Neuronal uptake is necessary for the hypotensive action of guanethidine. It competes for the norepinephrine storage site and, in time, replaces the natural neurotransmitter. This is the basis of its hypotensive effect. Drugs that prevent reuptake by the neurons, such as cocaine, would destroy the effectiveness of guanethidine... 

Those vesicles have been primed by docking at the active zone and are therefore ready for exocytosis upon arrival of an action potential. However, for the synapse to respond rapidly and repeatedly under heavy physiological demand, these exocytosed vesicles must be rapidly replaced. This is accomplished first from the recycled pool of vesicles and, as the demand increases, from the reserve pool. To be recycled, synaptic vesicles must be reloaded quickly after they release their contents. The sequence of events that is triggered by neurotransmitter exocytosis is known as the synaptic vesicle cycle [73,74] (Fig. 9-8). 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

The pathology of Parkinson s disease is associated with a substantial reduction in neurotransmitters such as dopamine, 5-hydroxytryptamine, GABA, in the brain. Treatment is based on the use of replacement of dopamine or dopamine agonists which relieve the rigidity but do not affect a cure. Currently, there is no laboratory-based diagnostic test for PD and so diagnosis is based on clinical presentation alone. 

Mechanism of Action An electrolyte that is essential for the function and integrity of the nervous, muscular, and skeletal systems. Calcium plays an important role in normal cardiac and renal function, respiration, blood coagulation, and cell membrane and capillary permeability. It helps regulate the release and storage of neurotransmitters and hormones, and it neutralizes or reduces gastric acid (increase pH). Calcium acetate combines with dietary phosphate to form insoluble calcium phosphate. Therapeutic Effect Replaces calcium in deficiency states controls hyperphosphatemia in end-stage renal disease. 

---