Central nervous system structure-activity relationships

Side Effects a.nd Toxicity. Adverse effects to the tricyclic antidepressants, primarily the result of the actions of these compounds on either the autonomic, cardiovascular, or central nervous systems, are summarized in Table 3. The most serious side effects of the tricyclics concern the cardiovascular system. Arrhythmias, which are dose-dependent and rarely occur at therapeutic plasma levels, can be life-threatening. In order to prevent adverse effects, as well as to be certain that the patient has taken enough drug to be effective, the steady-state semm levels of tricyclic antidepressant dmgs are monitored as a matter of good practice. A comprehensive review of structure—activity relationships among the tricyclic antidepressants is available (42). 

Biochemical effects of lead result in changes of the activity of enzymes, where lead may be bound to both functional and structural proteins or it can displace essential metals from biological molecules and destroy the structural function relationships of nucleic acids. The poisoning with lead can involve the haemopoietic system, central nervous system (encephalopathy), kidneys, gastrointestinal tract, cardiovascular system, etc. 

Because muscarinic receptors are involved in a variety of physiological processes in peripheral organs as well as in the central nervous system, numerous studies have been aimed at understanding the relationship between structure and activity of muscarinic agonists and antagonists. Better understanding of these relationships may eventually lead to the development of new drugs for specific diseases, such as Parkinson s disease and Alzheimer s disease. 

C = molar concentration of a drug CNS = central nervous system MR = molar refractivity P = partition coefficient PLS = partial least squares QSAR = quantitative structure-activity relationships. 

Hansch and coworkers, in their continuing attempts to place the discussion of structure-activity relationships of biologically active compounds on a mathematic basis, have presented evidence that the hypnotic activity of groups of barbiturates depends almost entirely on their relative lipophilic character as defined by their octanol-water partition coefficients. Although hypnotic activity was the model, the principle should apply to other actions of drugs in the central nervous system. 

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