Modulowanie funkcji układu cholinergicznego w leczeniu schizofrenii – dziś i jutro

Anna Frątczak; Katarzyna Kula; Jolanta Rabe-Jabłońska; Dominik Strzelecki

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Psychiatria i Psychologia Kliniczna

2013 | 13 | 2 | 108–115

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Modulowanie funkcji układu cholinergicznego w leczeniu schizofrenii – dziś i jutro

Authors

Anna Frątczak , Katarzyna Kula , Jolanta Rabe-Jabłońska , Dominik Strzelecki

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108-115 Psychiatria 2.2013 Fratczak Modulowanie.pdf

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Modulation of the cholinergic system function in the treatment of schizophrenia – today and tomorrow

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Abstracts

Recently, the interest in the cholinergic system in the pathogenesis of schizophrenia has increased. For many years the disorders in the function of this system, mainly as adverse effects induced by antipsychotics, have been observed. Perception of acetylcholine system evolves, which results from the assumption that the impact on the transmission through it may not only induce or eliminate the mentioned adverse effects but also directly modify symptomatology of schizophrenia. This article is aimed at a survey of the current literature on new options of the modulation of the cholinergic system functions. Presently the studies are focussed on searching for selective agonists and allosteric modulators of muscarinic receptors which can reduce the risk of side effects of the traditional antipsychotic therapy and simultaneously have their own therapeutic antipsychotic potential. The use of less selective substances does not yield such benefits. Psychopharmacologists’ interests cover also the modulators of nicotinic receptors α4β2 and α7, which favourably affect, among others, the cognitive functioning in patients with schizophrenia, as has been confirmed by many independent studies. Admittedly, in most of the patients, despite the treatment, adverse symptoms, cognitive deficits and often also residual positive symptoms persist. From the clinical point of view, significant are also adverse effects which often complicate the treatment, confine therapeutic abilities, and hamper the patient’s cooperation in pharmacotherapy. The studies on new, more selective cholinergic substances give some hope for improvements in schizophrenia therapy through increased efficacy and elimination of adverse symptoms.

W ostatnim czasie rośnie zainteresowanie rolą układu cholinergicznego w patogenezie schizofrenii. Od wielu lat obserwowano zaburzenia funkcji tego układu, głównie w postaci efektów niepożądanych wywołanych lekami przeciwpsychotycznymi. Postrzeganie układu acetylocholiny ewoluuje, co wynika z założenia, że wpływ na przekaźnictwo w jego obrębie może nie tylko wywoływać albo eliminować wspomniane objawy niepożądane, ale też bezpośrednio modyfikować symptomatologię schizofrenii. Celem niniejszego artykułu jest przegląd aktualnego piśmiennictwa dotyczącego nowych opcji modulowania funkcji układu cholinergicznego. Obecnie badania koncentrują się na poszukiwaniu selektywnych agonistów i allosterycznych modulatorów receptorów muskarynowych, które mogą redukować ryzyko skutków ubocznych tradycyjnej terapii przeciwpsychotycznej i jednocześnie mieć swój własny terapeutyczny potencjał antypsychotyczny. Zastosowanie substancji mniej selektywnych nie prowadzi do takich korzyści. W kręgu zainteresowań psychofarmakologów pozostają również modulatory receptorów nikotynowych α4β2 i α7, które korzystnie wpływają między innymi na funkcjonowanie poznawcze chorych na schizofrenię, co potwierdzono w wielu niezależnych badaniach. Jak wiadomo, u większości pacjentów mimo leczenia utrzymują się objawy negatywne, deficyty poznawcze, często też resztkowe objawy pozytywne. Z klinicznego punktu widzenia istotne pozostają także objawy niepożądane, które bardzo często komplikują leczenie, ograniczają możliwości terapeutyczne i pogarszają współpracę chorego w farmakoterapii. Badania nowych, bardziej selektywnych substancji cholinergicznych dają nadzieję na udoskonalenie terapii schizofrenii poprzez zwiększenie skuteczności i wyeliminowanie objawów niepożądanych.

Keywords

acetyl cholinesterase inhibitors allosteric modulators cholinergic system inhibitory acetylocholinesterazy ksanomelina modulatory allosteryczne schizofrenia schizophrenia układ cholinergiczny xanomeline

Discipline

MEDICINE: MEDICINE

Publisher

Medical Communications

Journal

Psychiatria i Psychologia Kliniczna

Year

2013

Volume

Issue

Pages

108–115

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