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Classical tricyclic antidepressants (TA), still regarded as essential in the treatment of depression, are called by pharmacologists "dirty" due to the complex (not "clean") mechanism underlying action of these drugs, involving several types of neurotransmission. Numerous side effects are connected with such a complex action. At the same time it should be noted that basic TAs are characterized by a considerable effectiveness, so that Imipramine is still used as a reference point (a "golden standard") in the evaluation of new drugs efficacy. One of major directions in the development of contemporary psychopharmacology of depression is the striving to synthesize drugs showing a selective effect on neurotransmission, to be precise – affecting a single, specific system (NA or 5HT). Implementation of such drugs in the clinical practice involves a number of questions, concerning: mechanisms underlying their antidepressant action, pathogenesis of depression (i.e. which of the two neurotransmission systems is disordered: NA or 5HT), and effectiveness of medications selectively enhancing a specific type of neurotransmission. These problems have not been elucidated so far, and research findings reported in the literature are inconsistent. Undoubtedly, antidepressants with selective action are safer than TAs – however, it is not clear yet whether they are equally effective. It can be hoped that these controversial problems may be settled due to the implementation in clinical practice of antidepressants affecting both the NA and 5HT systems, but having no influence on other types of neurotransmission (DA, ACh, Hl and H2 receptors). The latter group of drugs, interesting to theorists and promising to clinicians, require further controlled clinical trials and verification in a wide-range clinical practice. Above all, their therapeutic action should be compared with that of drugs selectively affecting neurotransmission.

The termination or serotoninergic neurotransmission is accomplished by rapid uptake or the released 5-HT by serotonin transporter (5-HTT). Activity 5-HIT is regulated by kinase C and phosphatase 2A. Changes in peripheral and central activity of 5-HIT (its uptake kinetic, Vmax and Km) are intensively studied. Many reports show modification in the binding of platelet presynaptic 5-HT uptake sites in psychiatric illnesses (with [3H]imipramine, [3H]paroxetine, [3H]citalopram used as ligands). This papers reviews some of the most important data from this field of research.

Six patients with endogenous depression were treated with imipramine (IMI). Serum concentrations or imipramine and its active metabolites were measured by FPIA method. Results were compared with received by HPLC met ode.

Fluoxetine is the best known antidepressant selectively suppressing serotonin reuptake (SSRI). Since the drug has been applied for over a decade, numerous studies could be carried out evidencing its effectiveness and safety in depressive syndromes of various etiology and clinical picture, in obsessive-compulsive disorders, and in bulimia. In the paper results of clinical trials and of meta-analyses are summarized. Reported results allowed not only to formulate more specific recommendations for the drug administration and to evaluate its side effects, but also to determine the risk of interaction.