Psychotropic Medications

The mechanism(s) of drug action are conventionally rationalized in terms of their binding as agonists or antagonists to specific proteins. However, for compounds acting on the membrane level other modes of action are also possible, owing to the principles of biomembrane operations as many body systems composed of lipids and associated proteins [72] .

Radicals such as superoxide radical anion, hydroxyl radical ('OH), and hydrogen peroxide (H2 O2) are produced in oxidative processes of cellular metabolism and accumulate in tissues upon aging as well as under pathophysiological conditions such as inflammation, leading to a state known as oxidative stress. These compounds are highly reactive toward cellular macromolecules, unsaturated lipids in particular, and their overproduction has been linked with several major diseases such as cancer, diabetes, schizophrenia, and neurodegenerative disorders, most notably both Parkinson's and Alzheimer's disease [72].

The changes in the chemical composition of the lipid bilayer caused by phospho-lipid peroxidation include shortening of the acyl chains and a decrease in the degree of their unsaturation, together with the modification of the acyl chains by polar car-bonyl, carboxyl, hydroxide, and peroxide moieties. The above can be readily expected to result in alterations in several key physical properties of the bilayer, including lipid-lipid interactions, the polarity profile, chain order, lateral pressure profile, as well as thermal phase behavior, lateral organization, and membrane asymmetry. These modifications of the membrane lipid matrix can be anticipated to modulate the functions and lipid interactions of the various membrane-associated proteins in addition to possible ROS-induced direct chemical modification of the proteins themselves [72].

Increased oxidative stress has been associated with the pathogenesis of tardive dyskinesia and other extrapyramidal side effects of the antipsychotic treatment of schizophrenia. Chronic exposure to chlorpromazine been shown to decrease the expression and activity of key antioxidant enzymes and to elevate the level of lipid peroxides in rat brain [72] .

Selective serotonin reuptake inhibitors can impair semen quality and damage sperm DNA integrity. In men with normal semen parameters, paroxetine induced abnormal sperm DNA fragmentation in a significant proportion of subjects, without a measurable effect on semen parameters. The fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity. In fact, it has been suggested that treatment with selective serotonin reuptake inhibitors may be associated with an increase in sperm having DNA damage, as assessed by the SCSA assay. In vitro exposure to estradiol, by-products of estrogen metabolism, or genistein increased damage to the human sperm DNA, possibly by causing oxidative damage [72] .

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