Stereospecific effect of flupenthixol on neuroreceptor gene expression.
An experimental method to test the hypothesis that antipsychotic (neuroleptic) agents influence gene expression in the mouse brain has been developed using the cis and trans stereoisomers of flupenthixol. The cis form of the drug is known to be clinically effective against some of the psychotic symptoms of schizophrenia as opposed to the trans isomer which is relatively inactive. A 2- to 3-fold increase in the abundance of dopamine 2 receptor mRNA was observed in the cis treated mice after a period of ten weeks. No change was observed in the expression of the dopamine D2 receptor gene upon treatment with the trans isomer. No change in the amount of 5-HT1A, 5-HT1C, alpha 1 adrenergic, beta 1 and beta 2 adrenergic neuroreceptor mRNA was found in the mice treated with active drug. The results show a long-term adaptation to D2 antagonism at the level of gene expression which occurs over a similar time scale to that of the clinical response to neuroleptic treatment of schizophrenia.[1]References
- Stereospecific effect of flupenthixol on neuroreceptor gene expression. De La Concha, A., McKie, J., Hodgkinson, S., Mankoo, B.S., Gurling, H.M. Brain Res. Mol. Brain Res. (1991) [Pubmed]
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