A. Facchi, G.D. Kotzalidis, P. Pancheri - Vol. 7, Giugno 2001, num.2
Testo Immagini Bibliografia Summary Riassunto Indice
L’importanza
del blocco dei recettori dopaminergici D3 e D4 nel trattamento della schizofrenia
The relevance of dopamine D3 and D4 receptor blockade for the treatment
of schizophrenia
Recent reformulations of the dopaminergic theory of schizophrenia tend to view the classical D2 receptors as responsible for extrapyramidal side effects and involve increasingly other neurotransmitter systems and the newly discovered receptors of the D2 family, the D3 and D4 receptors. Unfortunately, there are no drugs selective and specific for these receptors, so it is difficult to test the hypotheses of their implication in schizophrenia. The localization of D3 receptors is more compatible than that of D4 receptors with an involvement in this disease. Genetic studies on receptor gene polymorphisms are less negative for the D3 than for the D4 receptors. Clinical studies do not offer clues as to the involvement of these receptors in the pathophysiology of schizophrenia, since drugs possessing D3 receptor antagonist activity, such as amisulpride, possess considerable anti-D2 receptor activity, such to prevent the possibility to draw conclusions, and the only "pure" D4 receptor-specific antagonist tested in the human, L-745,870, behaves like an agonist towards the D4.4 subtype; this could account for the fact that this drug was not better than placebo and even worsened some patients; fananserin is active also on 5-HT2A receptors and shows only modest efficacy; nemonapride is effective, but is blocks also D2 and D3 receptors.