Effects on the Central Nervous System

The spontaneous electrical activity of the brain can be measured by electroencephalography (EEG), a technique that has been widely employed to study neurotoxic effects of chemicals both in humans and in experimental animals. EEG waves represent summated synaptic potentials generated by the pyramidal cells of the cerebral cortex (Misra 1992). These potentials are the responses of cortical cells to rhythmical changes arising from thalamic nuclei. The signals recorded can be separated into frequency bands—faster waves exceeding 13 Hz, and slower ones below 4 Hz. 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

Organic Pollutants An Ecotoxicological Perspective, Second Edition 

Morphine A Naturally Occurring Analgesic Effects on the Central Nervous System 

Thalamocortical radiation Salicylate Derivatives Ventrolateral nucleus of thalamus 

Sensory descending roof of trigeminal Extramedullary tumor (Central pain) 

Local segmental pain (Compression of post, root) Iff Remote pain through spinothalmic tract Subarachnoid block (Bupivacaine) 

Pain referred from visceras to skin supplied by same spinal segment Peripheral nerve block (Bupivacaine) 

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C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

Both Cushny and Dale found the amorphous gelsemium alkaloids represented by such fractions as gelseminine much more active than gelsemine. Cushny stated that gelseminine resembled coniine in action and showed a greater depressant effect on the central nervous system, but unlike coniine it exerted no pressor effect. It was also a powerful mydriatic. Dale found that 0-001 gm. of the hydrochlorides of the amorphous alkaloids injected into rabbits caused death from respiratory failure in 25 minutes, preceded by convulsions. These results are explained by the subsequent isolation from such amorphous fractions, of the potent alkaloids sempervirine and gelsemicine. 

Procarbazine causes myelosuppression, hypnotic and other effects on the central nervous system, e.g., vivid nightmares. Also, procarbazine causes a disulfiram like syndrome on ingestion of ethanol. 

The substance is irritating to the eyes, the skin and the respiratory tract. The substance may cause effects on the central nervous system, resulting in impaired functions. Exposure may result in death. The effects may be delayed. Medical observation is indicated. 

Tharion, WJ, McMenemy, DJ and Rauch, TM (1994) Antihistamine effects on the central nervous system, cognitive performance and subjective states. Neurophsychobiol. 29 97-104. 

Although research has been suggestive of caffeine modulated increases in muscular contractions leading to hand tremor, it is more likely that the hand tremor response is the result of caffeine s effects on the central nervous system.32 There is even evidence that moderate doses of caffeine may actually diminish muscle tone.32... 

Ginseng Rg2 has shown inhibitory effects on platelet aggregation similar to aspirin, and R0 reportedly inhibits the conversion of fibrinogen to fibrin [27]. The amount of ginseng administered may also influence the effect(s) produced. In rats and mice, small doses of ginseng extract result in increased spontaneous motor activity, whereas larger doses produce an inhibitory effect on the central nervous system [28]. 

Since nicotine has wide ranging effects on the central nervous system it seems likely that pharmacogenomic effects on the development of nicotine dependence will span several neurotransmitter systems. One study found an association between a polymorphism in dopamine /1-hydroxylase and level of tobacco consumption [20]. This enzyme is important in noradrenaline synthesis and it is tempting to speculate that genetically regulated variations in activity might influence susceptibility to nicotine withdrawal symptoms mediated by noradrenergic pathways, but more information is required on the molecular effects of the polymorphism. 

At 60 mg/L, HCN had only a slight depressive 17 effect on the central nervous system at 80 and 150 mg/L, severe CNS depression and incapacitation occurred... 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

The symptoms that followed the daily intramuscular administration of D.F.P. for 5 days mimicked most of the muscarine-like and nicotine-like effects (see p. 37) of cholinergic drugs. There were also effects on the central nervous system. 

Among the effects on the central nervous system the following symptoms were pronounced excessive dreaming, insomnia, nightmares and headaches. 

The hypotensive action of clonidine could not be explained satisfactorily by effects on the peripheral circulation. Numerous studies therefore considered the possibility of an effect on the central nervous system. Investigations performed on spinalized animals could... 

As reviewed in this chapter, a number of plants are recognized for their stimulant effects on the central nervous system. Although they work through a variety of neurochemical mechanisms, they all convergently alter neuromodulatory systems to produce a common effect. 

Many simple molecules have profound effects on the central nervous system. Several of these are drugs of abuse methamphetamine, cocaine, and heroin, among others. 

Cocaine readily penetrates mucous membranes and is an effective topical local anaesthetic that demonstrates intensive vasoconstrictor action. It has stimulant effects on the central nervous system and is a drug of addiction. It causes agitation, dilated pupils, tachycardia, hypertension, hallucinations, hyperthermia, hypertonia, hyperreflexia and cardiac effects. 

Diquat poisoning is much less common than paraquat poisoning, so that human reports and animal experimental data for diquat poisoning are less extensive than for paraquat. However, diquat has severe toxic effects on the central nervous system that are not typical of paraquat poisoning (Vanholder et al. 1981 Olson 1994). 

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