Serotonin drugs acting

Many psychoactive drugs act to alter neurotransmitter functions either through effects on their synthesis, metabolism or reuptake or by directly affecting the receptors for naturally occurring compounds. For example, drugs such as prozac increase serotoniner-gic activity by selective serotonin reuptake inhibition (SSRI). 

The problem is that all drugs exert a number of different effects, some of which are wanted and some of which are not (the side effects). In researching the activity of fluoxetine (Prozac), scientists noticed a discrepancy between the time the drug acts on serotonin transporters and the time at which the patient s symptoms are relieved. Many patients do... 

The large majority of antipsychotic drugs act mainly as dopamine receptor antagonists reducing the excess responsiveness to that neurotransmitter present in psychoses. It was found a decade ago that antagonists of serotonin H2 showed promising antipsychotic activity in several model systems. These dmgs would be better tolerated than their predecessor since they should be devoid of side effects... 

This syndrome most often occurs as a result of the interaction of two or more drugs acting via different mechanisms to potentiate the central effects of serotonin at 5-HTi receptors in the brainstem and spinal cord (490). It consists of the following symptoms ... 

Serotonin is present in a variety of sites in the brain. Its role as a neurotransmitter and its relation to the actions of drugs acting in the central nervous system are discussed in Chapters 21 and 30. Serotonin is also a precursor of melatonin in the pineal gland (Figure 16-2 ... 

In terms of the noradrenergic system, this chapter has described the locus co-eruleus as that part of the brain containing the noradrenergic neurons that mediate some of the symptoms of anxiety through alpha 2 and beta adrenergic receptors. Our discussion has also extended to the role of serotonin in anxiety, which appears to be key, yet quite complex and incompletely understood. One current theory developed in this chapter is the notion that anxiolytic drugs act as partial agonists at serotonin 1A receptors. 

By the mid-60s there was a strong consensus that depression, at least in its severe endogenous form, was caused by an abnormal biochemical state consisting of reduced levels of monoamines in the brain. The theory was set out systematically in a well-known paper by Schildkraut (1965), who concentrated on the role of noradrenalin (Schildkraut 1965). Other authors focused on serotonin (Coppen 1967). Schildkraut asserted that some if not all depressions are associated with an absolute or relative deficiency of catecholamines, particularly norepinephrine. .. elation may conversely be associated with an excess of such amines (Schildkraut 1965, p. 509). The primary justification for the theory was the belief that stimulants and antidepressant drugs acted to increase monoamine levels. Schildkraut referred to how the supposed efficacy of imipramine had initially cast doubt on the theory, but the riddle had been solved by Axelrod s research on its ability to block tissue reuptake of noradrenalin. 

Q4 (B)These drugs act by blocking serotonin reuptake at synapses, thus increasing the level of serotonin at the synaptic junction. In increase in the level of serotonin may diminish the repetitive behaviours. 

There is a great deal of evidence that deficiency of serotonin (5-hydroxytryptamine) is a factor in depressive illness, and many antidepressant drugs act to decrease its catabolism or enhance its interaction with receptors. A key enzyme involved in the synthesis of serotonin (and the catecholamines) is aromatic amino acid decarboxylase, which is pyridoxal phosphate-dependent. Therefore, it has been suggested that vitamin Be deficiency may result in reduced formation of the neurotransmitters and thus be a factor in the etiology of depression. Conversely, it has been suggested that supplements of vitamin Be may increase aromatic amino acid decarboxylase activity, and increase amine synthesis and have a mood-elevating or antidepressant effect. There is little evidence that vitamin Be deficiency affects the activity of aromatic amino acid decarboxylase. In patients with kidney failure, undergoing renal dialysis, the brain concentration of pyridoxal phosphate falls to about 50% of normal, with no effect on serotonin, catecholamines, or their metabolites (Perry etal., 1985). 

Metoclopramide is a first-generation benzamide. The drug acts presynaptically, mainly as a 5-hydroxytryptamine (5-HT serotonin) 5-HT4 receptor agonist and 5-HT3 receptor antagonist but it is also an antagonist at dopamine 1 (Dj) and 2 (D2) receptors (MacDonald 1991). The net effect of the interactions with these receptors is to facilitate acetylcholine release from enteric neurons and promote smooth muscle contrachon. Metoclopramide... 

All of the existing antidepressant drugs act through monoaminergic mechanisms, and further refinements are still possible in this arena. The concept of developing dual norepi-nephrine/serotonin uptake inhibitors, claimed for venlafaxine, has been adopted by other companies. Compounds with this profile are being developed by Eli-Lilly [duloxetine (50)]... 

Although the prevailing concept is that schizophrenia is due to hyperdopaminergic activity in the CNS,, not all antischizophrenic drugs act as DA antagonists some instead modify serotonin function. -... 

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