Therapeutic possibilities of cysteamine in the treatment of schizophrenia.
Schizophrenia has complicated pathogeneses that is not able to be explained by any one supposed hypothesis, although alterations in dopamine neurotransmission have been widely accepted as the most plausible mechanism. A transition from traditional typical antipsychotics to contemporary atypical antipsychotics which have significantly improved tolerability and enhanced specific efficacy has been also made based on this dopamine hypothesis. Cysteamine is a natural product of mammalian cells and found to be useful pharmacological alternative. A number of evidence suggests that cysteamine may control directly or indirectly dopamine neurotransmission in nucleus accumbens and other schizophrenia-related brain regions. Systemic cysteamine injection mitigated the apomorphine-induced stereotypy as well as decreasing motor stimulant effects of amphetamine, which favor cysteamine over animal models of schizophrenia relative to hyperactivity of dopaminergic pathway. In addition, cysteamine showed neuroprotective effects by way of enhancing central and serum brain derived neurotrophic factor (BDNF) that has been proved to be altered in patients with schizophrenia. Antipsychotic drugs exert their effect partly by modifying the synthesis and distribution of BDNF in selected brain region. Cysteamine was effective to reverse a disruption in prepulse inhibition, an endophenotypic marker of schizophrenia. Cysteamine can also stimulate the release of cortical dopamine, which is interesting in that decreased dopaminergic function in the cerebral cortex has been repeatedly demonstrated in patients with schizophrenia and associated with prominent depressive and negative symptoms. Cysteamine can also increase an important antioxidant, glutathione. Finally, cysteamine treatment was found to decrease weight gain, cataleptic behavior, and serum prolactin levels, which are the major beneficial properties of contemporary atypical antipsychotics. Hence, further explorations of therapeutic implication of cysteamine for schizophrenia in preclinical studies should be warranted in future.
Pae
Chi-Un
CU
Department of Psychiatry, Kangnam St. Mary' Hospital, The Catholic University of Korea, College of Medicine, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, South Korea. pae@catholic.ac.kr
Lee
Chul
C
Paik
In-Ho
IH
D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003543:Cysteamine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D008954:Models, Biological; D008959:Models, Neurological; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D003543:Cysteamine; D004298:Dopamine