Therapeutic mechanisms

Determining the underlying therapeutic mechanisms of a drug makes pharmacology a powerful tool for understanding biological phenomena. This chapter reviews the preclinical evidence of the impact of some neurotransmitter systems and related drugs on sleep and wakefulness. 

Whatever the therapeutic mechanism of action of Li+ is, the facts are that Li+ does indeed inhibit the turnover of the phosphoinositide cycle and does alter the levels of both second messengers, Ins(l,4,5)P3 and DAG, either or both of which may have wide-reaching secondary effects. 

The second popular hypothesis for the therapeutic mechanism of action of Li+ is its interference with another receptor-coupled, second messenger system, that of the plasma-membrane bound enzyme, adenylate... 

Li+, at therapeutically relevant concentrations, is a potent inhibitor of norepinephrine-stimulated adenylate cyclase activity ex vivo in both rat [133] and human brain [134], and it inhibits norepinephrine-stimulated cAMP accumulation in Li+-treated patients. Li+ also inhibits dopamine-stimulated cAMP accumulation in rat brain [135]. These inhibitory effects of Li+ have been shown to be region specific within rat brain, a fact that has obvious significance for a therapeutic mechanism of action. It is interesting that other antimanic drugs may also have dampening effects on dopaminergic neurotransmission. 

The discovery of psychopharmacological medications was revolutionary because they provided a means of treating illnesses that were otherwise intractable. With the exception of electroconvulsive treatments for severe depression, there were no medical treatments for disorders that did not respond to psychotherapy. Once established, the drugs led to an ongoing search for more effective and safer medications. A second reason for their revolutionary status is that they furthered understanding of mental illnesses and normal brain function. Investigations of their therapeutic mechanisms led to theories of the neurochemical bases of mental illnesses. 

Although the therapeutic mechanisms of various mood stabilizers are unknown, studies have concentrated on the following ... 

The major current working hypothesis for lithium s therapeutic mechanism of action supposes that its effects on phosphoinositol turnover, leading to an early relative reduction of myoinositol in human brain, are part of an initiating cascade of intracellular changes. Effects on specific isoforms of protein kinase C may be most relevant. Alterations of protein kinase C-mediated signaling alter gene expression and the production of proteins implicated in... 

Are Antlpsychotlcs with Multiple Therapeutic Mechanisms Better than Selective Dopamine 2 Antagonists ... 

Although it is not yet clear why the various atypical antipsychotics differ from each other, the answer is most likely to be found in the pharmacologic properties, other than serotonin 2A dopamine—2 antagonism, that they do not share in common. Although some of these properties are still unknown, many of them are known (and are shown in Figure 11—34 and in the individual icons for the various atypical antipsychotics discussed later in this chapter). Of the 17 pharmacologic properties detailed in these icons, some undoubtedly mediate side effects, and others may mediate additional therapeutic actions mentioned here. This raises the question Are atypical antipsychotics with multiple therapeutic mechanisms better than those with fewer therapeutic mechanisms (see Fig. 11-35) This theme of multiple pharma-... 

Perhaps psychopharmacological treatments for psychotic disorders in the future will need to borrow a chapter out of the book of cancer chemotherapy and HIV/ AIDS therapy, in which the standard of treatment is to use multiple drugs simultaneously to attain therapeutic synergy. Combination chemotherapy for malignancy uses the approach of adding together several independent therapeutic mechanisms. When successful, this results in a total therapeutic response that is greater than the sum of its parts. 

Templeton NS (ed) (2008) Gene and cell therapy therapeutic mechanisms and strategies. Marcel Dekker, New York... 

Meanwhile, researchers and medical publicists continue to spin SSRI-induced abnormal neuronal growth as evidence of a therapeutic mechanism. A December 19, 2005, headline in a promotional bulletin called Johns Hopkins Medicine declared, Popular Antidepressants Boost Brain Growth, Hopkins Scientists Report. From the university s Office of Corporate Communications, this Johns Hopkins public relations release boasted about a newly published study by the medical center (Zhou et al., 2006). 

Therapeutic Mechanisms and the Type-1/Type-2 Imbalance in Schizophrenia and Depression... 

Force T, Kerkela R (2008) Cardiotoxicity of the new cancer therapeutics - mechanisms of, and approaches to, the problem. Drug Discov Today 13 778-784... 

In conclusion, most but not all differences will disappear and indeed, from such diversity, there may spring new understanding of both clinical and therapeutic mechanisms for the development and applicability of better medications. 

Key words Pharmacogenomics, Atherosclerosis, Therapeutic targeting, Therapeutic mechanisms,... 

The xanthine theophylline has been used for several decades in the treatment of asthma. This compound produces different effects at the cellular level, including phosphodiesterase isoenzyme inhibition, adenosine antagonism, catecholamine secretion enhancement, and the modulation of calcium fluxes. Recently, theophylline was found to have both immunomodulatory and anti-inflammatory properties therefore, interest in its use in patients with asthma has been renewed [103]. Recent studies have thus discovered that at low doses, theophylline is able to decrease airway inflammation, accelerate eosinophil apoptosis, and decrease recruitment of lymphocytes and neutrophils to the lungs. Although it is classified as a phosphodiesterase inhibitor, its exact therapeutic mechanism of action remains undetermined [104]. Of the new mechanisms that have been included in the potential mode of action of theophylline, one is the apoptosis of inflammatory cells. In eosinophils and lymphocytes, for example, this effect is due to the compound s ability to inhibit phosphodiesterase, which leads to an even more pronounced increase in intracellular cAMP levels than that which occurs when adenylate cyclase, the enzyme that synthesizes cAMP, is activated. This inhibition and the resulting cAMP level increase thus lead to... 

For a long time, anticholinergic drugs were the only effective treatment of parkinsonian symptoms. The therapeutic mechanism of these drugs is suppression of the relative cholinergic overactivity in the striatum of parkinsonian patients. 

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