Antagonism multiple

There is also preliminary data that risperidone, an atypical antipsychotic that antagonizes multiple receptor types including dopamine receptors and serotonin receptors, may affect certain ERP components. A study of chronic risperidone delivery via subcutaneous implants reported increased P20 amplitude but no effects on the N40 component. Risperidone in this study was unable to block the amphetamine-induced decreases in the P20 component, but attenuated amphetamine-induced reduction of the N40 (Siegel et al., 2004). 

Brzostowski, J. A., Parent, C. A., and Kimmel, A. R. (2004) A Ga-dependent pathway that antagonizes multiple chemoattractant responses that regulate directional cell movement. Genes Dev. 18, 805-815. 

Competitive, noncompetitive, and allosteric antagonism can be discerned from the pattern of multiple displacement curves. 

FIGURE 9.18 Multiple receptor effects (ordinates denote pK values for antagonism or receptor occupancy) of (a) yohimbine and (b) amitriptyline. 

Nitric oxide, a vasodilatory hormone released by the endothelium, is found in higher concentrations in HF patients and provides two main benefits in HF vasodilation and neurohormonal antagonism of endothelin.9 Nitric oxide s production is affected by the enzyme inducible nitric oxide synthetase (iNOS), which is up-regulated in the setting of HF, likely due to increased levels of angiotensin II, norepinephrine, and multiple cytokines. In HF, the physiologic response to nitric oxide appears to be blunted, which contributes to the imbalance between vasoconstriction and vasodilation. 

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Molecular genetic techniques have confirmed the existence of multiple subtypes of p-adrenoceptors. Pi-Receptors and Pj-receptors have been cloned, and recent molecular biological evidence indicates the existence of at least one additional p-receptor sub-type, called the p3-receptor. It is suggested that the P3-receptor may mediate some of the metabolic effects of catecholamines, although no available p-blocker has been shown to rely on Pa-receptor antagonism for its therapeutic effectiveness. 

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-... 

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