V.A. Voicu 1, 2, F. Rădulescu 3, M.D. Gheorghe 1
1 Catedra de Farmacologie, Toxicologie şi Psihofarmacologie Clinică, Facultatea de Medicină, Universitatea de Medicină şi Farmacie „Carol Davila”, Bucureşti, România
2 Centrul de Cercetări Ştiinţifice Medico-Militare, Bucureşti, România
3 Facultatea de Farmacie, Universitatea de Medicină şi Farmacie „Carol Davila”, Bucuresti, România
Abstract
The authors present in synthesis the antipsychotics mechanisms consecutive to the interaction with neurotransmission systems receptors, respectively the dopaminergic, serotoninergic, cholinergic system etc. Implicitly, a brief review is performed, by means of the pharmacological proofs of schizophrenia pathogenic theories. Another domain approached hints the ethio-pathogenic aspects of schizophrenia as the background of potential pharmacological targets – genetic components and impact of the factors perturbing the neurodevelopment and neurodegeneration processes initiated in a favorable context. The antipsychotics effects correlations are analyzed at the level of various receptors with the therapeutic effects on one side which can be the direct consequence of action on receptor or indirect consecutive to counter-regulations determined in other neuromediation systems, and on the other side these effects can be relatively immediate (of hours – days order) or slowly installed (weeks) or do not appear at all (resistance to treatment, non-responders etc.). In this context two concepts are brought into discussion: the therapeutic effects with immediate onset and defined after 2-3 weeks and slow effects becoming marked after around one month and defined or not after few months. Another type of arguments are also brought into discussion: the slow and late effects of antidepressant, the addiction phenomenon installation as a complex process of neuroadaptation, but also the experimental and clinical proofs that the antipsychotics induce complex phenomenon on the cerebral structures. In fact in the context of chronic treatment with antipsychotics, the brain also behave following the known rules: it launches short latency, rapid processes with homeostatic destiny and initiating a series of other, more slow reactions implying protein and receptor synthesis, synaptic plasticity, neuroplasticity, neurogenesis etc. These processes implying the changes of some genes expression are approached as epigenetic phenomenon conferring to the organism, on one side, flexibility and adaptability and, on the other side, the genetic stability. In this context, the authors are appreciating that there are some convincingly arguments (direct or indirect) in order to admit that the antipsychotic – pathogenic psychotic processes two successive independent and correlated phases are envisaged: the pharmacodynamic phase in which the active compound determines the known effects consecutive to antagonizing or activation of receptors for which it has affinity and the pharmacotherapeutic phase implying more slow complex processes. The rapid counter-regulations of the interconnected neurotransmission systems are part of the phenomenon probably initiating slower and more complex reactions implying compensatory phenomenon in a positive or negative sense (up or down-regulation) at the level of receptors, neuromediators synthesis, synaptic connections or even appearance of new neurons in some cerebral regions. This second phase will outline the final therapeutic response which will install in weeks, months and in connection with the rearrangement and resetting between different neurotransmission systems (affected in the schizophrenia context) on the basis of the presented epigenetic processes, we will report or not an individual therapeutic effect.