Transmitters drugs affecting

If one considers H3 receptor agonists as potential drugs, one has to realize that H3 heteroreceptor-mediated effects are frequently small or moderate. In addition, one has to take into consideration that the release of at least six transmitters is affected and that the effects occur in at least six regions of the CNS (Fig. 1). On the other hand, it is so far unknown whether all the examples of H3 heteroreceptors identified in animals also occur in humans. Moreover, one must be cautious when extrapolating from in vitro data to the situation in vivo. To give an example. Clonidine, which affects presynaptic a2-adrenoceptors on several types of neurones and in a variety of CNS regions, became a very useful drug for the treatment of essential hypertension and for some other indications. 

Nefopam is a centrally acting non-opioid analgesic used for mild to moderate pain its mechanism of action is uncertain but may be due to an inhibition of serotonin, noradrenaline and dopamine reuptake. It is considered by some to act on GABA B receptors and is likely to interact with other drugs affecting these neuro transmitters,... 

The type of response normally elicited by glutamate, GABA, ACh, dopamine, norepinephrine, serotonin (5HT), and the opioid peptides and the modulations induced by drugs affecting the receptors relevant to each of these transmitters is succinctly presented. 

Figure 5.5 Diagrammatic representation of a synapse showing the sites at which drugs may act to increase or decrease the concentration and action of a neurotransmitter. Drugs can affect the synthesis (1), storage (2), release (3), action (4) and destruction (5) of the transmitter. The different ways in which they achieve this (a, b, c) are outlined in Table 5.1...

In neurochemical terms, amphetamine and cocaine boost monoamine activity. Amphetamine has a threefold mode of action first, it causes dopamine and noradrenaline to leak into the synaptic cleft second, it boosts the amount of transmitter released during an action potential and third, it inhibits the reuptake of neurotransmitter back into presynaptic vesicles. These three modes all result in more neurotransmitter being available at the synapse, thus generating an increase in postsynaptic stimulation. Cocaine exerts a similar overall effect, but mainly by reuptake inhibition. The main neurotransmitters affected are dopamine and noradrenaline, although serotonin is boosted to a lesser extent. These modes of action are outlined in Chapter 3, and the neurochemical rationale for drug tolerance is covered more fully in Chapter 10. The main differences between amphetamine and cocaine are their administration routes (summarised above) and the more rapid onset and shorter duration of action for cocaine. 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

Depression. Depression is our most common mental problem. One in four women and one in ten men will have a major depression during their lifetime.1095 More than 15 million people in the United States are affected by severe depression in any given year and more than 30,000 may commit suicide.1096 1097 Worldwide psychiatric problems, mostly depression, account for 28% of all disabilities.1098 The biogenic amine hypothesis states that depression results from the depletion of neurotransmitters in the areas of the brain involved in sleep, arousal, appetite, sex drive, and psychomotor activity. An excess of transmitters is proposed to give rise to the manic phase of the bipolar (manic-depressive) cycle that is sometimes observed. In support of this hypothesis is the observation that administration of reserpine precipitates depression, which may be serious in 15-20% of hypertensive patients receiving the drug. Similar effects are observed with the dopa decarboxylase inhibitor a-methyldopa... 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

Neuropharmacology is the study of drugs that affect the nervous system and its neuronal components. The functions of the nervous system are intimately linked with the synthesis, storage, release, and uptake of many transmitters and their modulators. The beneficial effects or side effects of an extensive number of drugs are brought about through their interaction with these neurotransmitter-neuromodulator systems. 

As mentioned previously, there are many potential targets available in nerve cells for interaction with a drug. Some targets are general to all nerve cells, and drugs that affect them will produce widely dispersed effects. Other targets are found only in a subset of nerve cells, and in these cases drug effects will be restricted to them. The most common reason specific interactions occur is that neurons differ in the transmitter system they possess. 

With the experience gathered, we now know that whilst the third limitation is correct, the situation with the first two is less clear. The drugs might also, indirecdy, favorably affect the levels of other transmitters (as well as in other possible ways, such as slowing down amyloid plaque accumulation). There is also evidence that in those patients who respond symptomatically, the rate of decline seems to be reduced [29,30]. 

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