Neurotransmitters clinical applications

The neurotransmitter dopamine has currently found clinical application in the treatment of cardiovascular collapse and shock. Treatment with dopamine-related drugs has been limited to such brain disorders as Parkinson s disease, schizophrenia, and hyperprolactinemias. Accumulating data from animal experiments, however, indicate the possible involvement of dopamine in other diseases and the potential use of dopamine agonists or antagonists in these disorders. Gastrointestinal disturbances (especially duodenal ulcer disease) seem to represent such a group of dopamine-sensitive alterations. 

The incorporation of glycosides into peptide neurotransmitters imparts drug-like character to the neurotransmitter message via membrane hopping . The importance of the gly-copeptide-membrane interaction is emphasized, and the biousian theory is briefly explained. Application of this approach to enkephalins, the endogenous opioid peptides, leads to potent analgesic compounds capable of systemic delivery. The clinical applications of these compounds are advocated by the author. 

Vasoactive intestinal peptide (VIP) is an extremely potent vasodilator but is probably more important as a neurotransmitter. It is found in the central and peripheral nervous systems and in the gastrointestinal tract. No clinical application has been found for this peptide. 

Substance P is another neurotransmitter peptide with potent vasodilator action on arterioles. However, substance P is a potent stimulant of veins and of intestinal and airway smooth muscle. The peptide may also function as a local hormone in the gastrointestinal tract. Highest concentrations of substance P are found in those parts of the nervous system that contain neurons subserving pain. At the present time, there are no clinical applications for substance P or its antagonists. However, capsaicin, the hot component of chili peppers, releases substance P from its stores in nerve endings and depletes the peptide. Capsaicin has been approved for topical use on arthritic joints and for postherpetic neuralgia. 

A departure from the catechol pattern of the natural neurotransmitters was achieved following application of the fact that arylsulfonamido hydrogens are nearly as acidic as phenolic OH groups. Nitration of p-benzyloxyacetophenone gave 18 which was reduced to 19 with Raney nickel and hydrazine, and in turn reacted with mesyl chloride to give sulfonamide 20. Methanesulfonate 20 was then transformed to soterenol (21), a clinically useful bronchodilator, in the... 

Strychnine, a very poisonous alkaloid to animals, binds to glycine receptors. Applications of strychnine can be considered only in clinical doses. Their purpose is to activate neurotransmitters in the spinal cord, which is generally suppressed by glycine. Strychnine competes only with glycine in the receptor. This alkaloid may be used to stimulate respiration and circulation in cases of physical weakness. Moreover, strychnine products are used in the treatment of eye and optic nerve disorders. Larger doses are lethal. 

Different compounds of clinical interest have been analysed in CE microchips with EC detection. Due to their favourable inherent characteristics, neurotransmitters [24,27,94,121] and ions [59,60,67,72,130] have been the class of choice for testing amperometric and conducti-metric detectors, respectively. Much research has focused on the separation and detection of these analytes and the number of references that can be found is broad [50]. Applications of amperometric or con-ductimetric detection for other analytes of clinical significance can be found in Table 34.1, where information about the microchip material, EC technique, electrode configuration as well as electrode material employed is included. 

L-dopa, a precursor of the neurotransmitters norepinephrine and dopamine, was introduced into HE therapy by J.D. Parkes et al. in 1970. The results were good. As yet, there is still no accepted opinion on the use of this substance. Piracetam, as a nootropic substance, led to a clear improvement in typical electrical brain activities in animals displaying hepatic damage and symptoms of encephalopathy. Similarly, a double-blind randomized cross-over study with the nootropic agent centropheno-xine partly showed positive effects in psychometric testing. Bromocriptine, an agonist of the dopamine receptor, was also used in 1980 for chronic hepatic encephalopathy. (146,163) Application of L-carnitine (6 g/day orally, divided into two doses, for 4 weeks) leads to a marked reduction of hyperammonaemia and a clear improvement in clinical symptoms of HE in cirrhotic patients. (119) (s. p.49)... 

Various topical agents have been tested. Capsaicin is an alkaloid and a main ingredient in chilli peppers, and is available in a cream for topical use. This neurotoxin depletes substance P from the terminals of unmyelinated C-fibres. Substance P is considered the primary neurotransmitter of pain from the periphery to the CNS. Data suggest that Capsacain application produces degeneration followed by reinnervation of epidermal nerve fibres. This in combination with inconsistent results from clinical trials as regards its efficacy for treatment of painful diabetic neuropathy has resulted in limitation of its use [37],... 

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