Transmitter Systems

Little has been done to examine other transmitter systems although aluminum has been shown to have some inhibitory effects on the synaptosomal uptake of dopamine, norepinephrine, and 5-hydrojtytryptamine. Wenk and Stemmer investigated the effect, in rats, of aluminum in combination with a number of special diets, many of which were deficient in other metals. The various interactions between the metals were complex and difficult to interpret in terms of the norepinephrine and dopamine levels examined. Animals fed an aluminum-contaminated, optimal nutrient diet, showed elevated norepinephrine levels in the cerebral cortex and hippocampus, while animals fed aluminum-contaminated laboratory chow showed reduced norepinephrine levels in the 

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There are now many examples of novel peptide transmitter systems that have been identified through orphan receptor ligand screening and greatly impacted the basic understanding of human physiology. Prime examples for the discovery of novel transmitter with therapeutic implications are the neuropeptides orphaninFQ/... 

A final, important distinction between sibutramine and (7-fenfluramine is that the actions of the former, but not the latter, rest on its modification of both 5-HT and noradrenergic transmission. Thus, the reduction in food intake by sibutramine is partially blocked by ai- or jSi-adrenoceptor antagonists as well as 5-HT2a/2C or 5-HT2b/2c antagonists. In fact, there appears to be a synergistic interaction between these two transmitter systems. This is illustrated by a study of the effects of the selective serotonin... 

Unlike other transmitter systems, there are no obvious meehanisms for dampening glutamate release. Presynaptic autoreceptors for glutamate are mostly of the kainate type (see below) and appear to act as positive rather than negative influenees on further release of the amino acid. Although poorly characterised at present, inhibitory autoreceptors of the metabotropic type of receptors may act to inhibit release of glutamate. 

An intriguing area of research on opioids has been the accumulating evidence for plasticity in opioid controls. The degree of effectiveness of morphine analgesia is snbject to modulation by other transmitter systems in the spinal cord and by pathological changes induced by peripheral nerve injury. Thus in neuropathic states, pain after nerve injury, morphine analgesia can be reduced (but can still be effective) and tactics other than dose-escalation to circumvent this will be briefly discussed in Chapter 21. 

In view of this neurotoxicity, we will review some data relevant to this process. First, we will review data showing that methamphetamine (METH), a prototypic psychomotor stimulant, which has been widely used for nonmedical purposes at doses often a good deal higher than therapeutie doses, is neurotoxic to dopamine (DA) and serotonin (5-hydroxytryptamine (5-HI)) systems. Second, we will examine the evidence that other substituted phenethylamines are also neurotoxic to certain transmitter systems. Last, we will examine the behavioral and pharmacological consequences of neurotoxicity that result from exposure to some of these amphetamine-related drugs. 

It was later determined whether this was a generalized response to METH of all transmitter systems or whether it was eharacteristic of speeifie systems. In the dosage used, METH did not affect striatal choline... 

Fig. 5.12 (a) Synaptic types along dendritic spines of M/T and GC units uni-, and bi-directional junctions, (b) Transmitter systems at a reciprocal synapse, Mitral-Granule cell junction. [Glu, glutamate (R, receptor) GABA, y-aminobutyric acid (R, receptor) E, intracellular effector and aAR, alpha-adrenergic receptor.]. (From Hayashi et al., 1993.)... 

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. 

Kombian SB, Warenycia MW, Mele FG, et al. 1988. Effects of acute intoxication with hydrogen sulfide on central amino acid transmitter systems. Neurotoxicology 9 587-595. 

Histaminergic neurons can regulate and be regulated by other transmitter systems 261... 

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

Persson SA, Cassel G, Sellstrom A. 1985. Acute cyanide intoxication and central transmitter systems. Fund Appl Toxicol 5 5150-5159. 

Future What transmitter systems best explain drug effects Are they aberrant in schizophrenia ... 

Monoamine Oxidase Inhibitors (MAOIs). The MAOls work in a unique fashion by blocking the activity of an enzyme that degrades each of three key brain transmitters norepinephrine, dopamine, and serotonin. These widespread effects on several brain transmitter systems make the MAOls a potentially very effective class of medications for a variety of disorders. A few small studies have evaluated the usefulness of the MAOls in the treatment of BPD and found them moderately helpful for the impulsivity associated with this illness. Unfortunately, the requirements for strict dietary restrictions due to a risk of hypertensive crisis severely limit the usefulness of MAOls in the treatment of BPD. These restrictions are a particular concern when treating patients who have problems with impulsivity and are therefore likely to have difficulty maintaining the dietary regimen. For this reason, although they may theoretically be helpful, MAOls should only be used to treat BPD after other more easily tolerated medications have been tried and have failed. In the near future, so-called reversible MAOls that appear to avoid the need for diet restrictions may become available. If so, this will allow us to reconsider their use in the treatment of BPD. For more information regarding the use of MAOls, please refer to Chapter 3. 

Anatomical and pharmacological studies have both indicated that the two major transmitter systems within the brain are the inhibitory GABA ergic and the excitatory amino acid (EAA) pathways [264]. At least four different receptors mediate the action of EAA, they are named according to the most selective li-... 

Characteristics of transmitter systems likely to provide network integration potentially generating consciousness include the following ... 

Alterations in consciousness induced by such plant chemicals include hallucinations or visions, experienced in euphoric trance-like states and often interpreted as spirit contact or possession, inspiration and enlightenment, self dissolution or cosmic union. As for traditional plant medicines, selection of plants of the gods and appropriate dosage was empirical, based—long before any neuropharmacological knowledge—on a process of trial and error. It is remarkable that identification of the active constituents of these plants in the last century has demonstrated interactions with key transmitter systems implicated in the neurobiology of consciousness. 

Sacred plants can be considered in neurochemical categories, according to how the active chemicals interact with specific transmitter systems. In some instances more than one system is implicated, and in others the plants are used in complex mixtures. Much of the following discussion on the different species, their uses and active chemicals, is derived from the highly informative books by Schultes and Hofmann (1992) and Devereux (1997), and ethnopharmaco-logical information not referenced is from these sources. 

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