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Sexual dysfunctions may be one of depressive symptoms as well as undesirable effects of some antidepressive agents' application. The article presents pathophysiological mechanisms connected with the influence of antidepressive drugs on particular stages of sexual reaction. Authors also presented drug strategies in cases of sexual dysfunctions as their spontaneous relief is rather a rare phenomenon.
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The second generation of antidepressants have been developed with the goal to reduce cardio-toxic effects and to further a more specific action on neurotransmitter systems. However some standardized actual parameters, clinical, biological and pharmacological may be accepted as reasonable elements in evaluating the therapeutic effects. Among them we will distinguish the diagnostic instruments which define categories of affective disorders; rating scales to assess gravity, the type of clinical test, duration of the test and finally those biological variables which should be an integral part of the evaluation of new antidepressants.
Genuine side effects of antidepressants are difficult to specify. Except for rare cases, imputability of a severe effect is questionable. However, several recent drug surveillance studies allow to better assess the tolerability of these compounds. The first is British: it compared the blood toxicity of mianserin and amitryptiline (Inman). The second (Henry) is based on the calculation of a lethal toxicity index (deaths per millions of prescriptions), varying with the different compounds. The third (Cooper) pools the data of all the comparative trials of fluoxetine as well as all the relevant effects noticed with this drug (more than 7,500 prescriptions in 1988). Antidepressants generally have to be used on a long term basis. The study of the safety of their long term use is absolutely necessary.
The metabolism of N-benzyl-piperazine-picolinyl fumarate (EGYT-475), a new antidepressant agent, was studied in rat and dog liver homogenate and microsomes. The metabolites were separated by HPLC technique. Quantitative analysis was performed using radioactive labelled form of EGYT-475. The metabolic pathways of EGYT-475 in both species involve hydrolysis in the piperazine-picolinyl part and oxidation of the benzyl group to benzoic acid. The rate of these transformations differs in the two species. The possibility of the formation of polar conjugates was also studied.
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