Neurotransmitters pharmacodynamics

The pharmacodynamic effects of ethanol are complex, and any attempt to link its actions to specific neurotransmitters or isolated brain regions is simplistic. A complicated neural network involved in the actions of ethanol accounts for its reinforcing, intoxicating, and abstinence effects. At the present time, use of medications that target neurotransmitters and neuromodulators affected by ethanol represents a reasonable strategy for the development of pharmacotherapies that reduce the reinforcing effects of alcohol and the craving and withdrawal symptoms that commonly occur in the context of alcohol dependence. 

The term pharmacodynamics encompasses all the processes that influence the relationship between drug concentration and resulting effects. Psychotropic drugs have a wide variety of targets within neuro transmitter systems, including neurotransmitter synthesis, degradation of enzymes, storage, receptors, and specific transporter proteins. 

Age-related variations in central nervous system (CNS) neurotransmitter production and receptor sensitivity are the most likely explanations for the pharmacodynamic differences observed between children and adults following administration of psychotropic medications [39a], Children have lower phenobarbital ratios than adults, and the ratio increases with gestational age [40,41]. Conversely, a lower therapeutic range for children has been identified for cyclosporine, phenytoin, and digoxin [42]. 

The pharmacodynamics are affected due to altered levels of neurotransmitters and receptors in the central nervous system with age. The blood-brain barrier may be less effective, hence the brain may be exposed to higher drug and toxin levels in elderly subjects (Toornvliet et al. 2006). 

For pharmacodynamic agents acting within one species (human), selectivity may also be achieved by differences in accumulation, when similar receptors are located in cells or in membranes of different character. The neurotransmitter receptors, for example, are similar, but are found in a variety of highly differentiated cells whose membranes are unlikely to possess the same physical characteristics. 

Because they are so reactive, even at small doses, most alkaloid-rich plants are used sparingly, if at all, in Western herbalism. Indeed, use of many of the alkaloidal species is restricted by law, or listed on poison schedules. However, alkaloids—either as isolated compounds or their semi-synthetic derivatives—are widely used in pharmaceutical medicines. Much of our understanding of the mechanisms of neurotransmitters and receptor sites comes from research into the pharmacodynamics of alkaloids. The widespread use of terms such as nicotinic and muscarinic receptors supports this idea. 

The pharmacodynamically complex profile of the ergolines as ligands for serotonin (5-HT) receptors, dopamine (D) receptors, and adrenoceptors, respectively, is explainable by the fact that these alkaloids include the essential structural features of the corresponding three monoamine neurotransmitters. This can be visualized by superimposition of the ergoline skeleton by these three natural agonists each (Fig. 4.9). 

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