Nervous system introduction

Noback, C. R., and Demarest, R. J. (1972) The Nervous System Introduction and Review, McGraw-Hill, New York... 

Compounds available in the United States are Hsted in Table 1. Whereas they vary in degree, all of them share similar HabiUties of cardiovascular side effects, the potential for central nervous system (CNS) stimulation, the development of tolerance, and abuse potential. AH, with the exception of ma2indol, are derivatives of phenethylamine. The introduction of an oxygen atom on the -carbon of the side chain tends to reduce CNS stimulant properties without decreasing the anorectic activity. Following the Federal Controlled Dmg Act of 1970, dmgs were classified into one of five schedules according to medical utiUty and abuse potential. 

Methods for visualizing individual neurons and glia in vivo have depended for more than 100 years on histo-chemical reactions with cytoskeletal elements and even now these methods have not been surpassed. Because cytoskeletal structures play a particularly prominent role in the nervous system, cytoskeletal proteins represent a large fraction of total brain protein, comprising perhaps a third or more of the total. In fact, much of our knowledge about cytoskeletal biochemistry is based on studies of proteins purified from brain. The aims of this chapter are twofold first to provide an introduction to the cytoskeletal elements themselves and second to examine their role in neuronal function. Throughout, the emphasis will be on the cytoskeleton as a vital, dynamic component of the nervous system. 

First, you will learn about the human nervous system and how it works when it is healthy. This will include an introduction to the structure (anatomy) of the nervous system and the function (physiology) of the nervous system. Next, we ll describe the things that can go wrong. We ll look at how the system breaks down and malfunctions. Then we ll show you how these breakdowns can result in psychiatric illness. Finally, we ll introduce you to the medications used to treat psychiatric illness. You will learn where these medications work and our best guess of how they work. The presumed mechanism of action of many medications is just that, presumed. In contrast to antibiotics, in which we know quite a lot about the ways that they kill bacteria or stop them from reproducing and how these mechanisms ultimately effect a cure for an infectious disease, less is known about how psychotropic medicines work. Oh, we pretty well understand what psychotropic medicines do when they reach the nerve cell. For example, most of the antidepressants used today block the reuptake of serotonin at the nerve cell, but we re still not sure why blocking serotonin reuptake gradually improves mood in someone with depression. This will lead to a tour, if you will, of what happens to a medication from the time the pill is swallowed, until it exerts its therapeutic effect. 

The last two decades have seen the introduction of several distinct functional imaging techniques that can be used to investigate centrally active compounds working in the brain in vivo. These techniques provide windows through which to observe phenomena in the intact and fully functional central nervous system. When applied to studies with human volunteers or patients one can obtain information that cannot be extrapolated from animal models, and from areas such as the brain and neurotransmitter systems that would otherwise be inaccessible in vivo. When combined with peripheral measurements and objective and subjective assessments of behavior, these methods can be used to explore how psychopharmaceuticals influence central nervous svtem activity and behavior. Moreover, compounds with a known mechanism of action can be employed as tools to understand how different elements of the central nervous system work. 

Section V. Drugs that Act in the Central Nervous System Chapter 21 Introduction to the Pharmacology of CNS Drugs... 

The structure-activity relationship is also demonstrated by an alternative experiment. Since the sedative property of a drug requires that the drug be transported directly to the nervous system, a decrease in hydrophobic bonding should result in an increase in sedative activity. The successive introduction of methyl groups to adamantane carboxamide (110) does result in a progressive increase in the sedative activity of the drug in mice 249 ... 

In this chapter a brief introduction to the nervous system is presented and its functions are described. A discussion of some of the mechanisms of structural and functional neurotoxicant effects follows. These descriptions are not exhaustive, they are meant to illustrate the concepts of toxicant interaction with the nervous system. Finally some methods for testing toxicant effects in the nervous system are explored. 

Choline esters are poorly absorbed and poorly distributed into the central nervous system because they are hydrophilic. Although all are hydrolyzed in the gastrointestinal tract (and less active by the oral route), they differ markedly in their susceptibility to hydrolysis by cholinesterase in the body. Acetylcholine is very rapidly hydrolyzed (see Chapter 6 Introduction to Autonomic Pharmacology) large amounts must be infused intravenously to achieve concentrations high enough to produce detectable effects. A large intravenous bolus injection has a brief effect, typically... 

The central nervous system contains both muscarinic and nicotinic receptors, the brain being relatively richer in muscarinic sites and the spinal cord containing a preponderance of nicotinic sites. The physiologic roles of these receptors are discussed in Chapter 21 Introduction to the Pharmacology of CNS Drugs. 

The role of muscarinic receptors in the central nervous system has been confirmed by experiments in knockout mice (see Chapter 1 Introduction). Predictably, carbachol did not inhibit atrial rate in animals with mutated M2 receptors. The central nervous system effects of the synthetic muscarinic agonist oxotremorine (tremor, hypothermia, and antinociception) were also lacking in mice with homozygously mutated M2 receptors. Knockout of Mi receptors is associated with different changes in the peripheral and central nervous systems. Oxotremorine did not suppress M current in sympathetic ganglia, and pilocarpine did not induce epileptic seizures in Mi mutant mice. 

As suggested in Chapter 6 Introduction to Autonomic Pharmacology, the Mi receptor subtype appears to be located on central nervous system neurons, sympathetic postganglionic cell bodies, and many presynaptic sites. M2 receptors are located in the myocardium, smooth muscle organs, and some neuronal sites. M3 receptors are most common on effector cell membranes, especially glandular and smooth muscle cells. 

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