alexa Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Proteomics & Bioinformatics

Author(s): Strange PG

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Abstract Interaction of the antipsychotic drugs with dopamine receptors of the D2, D3, or D4 subclasses is thought to be important for their mechanisms of action. Consideration of carefully defined affinities of the drugs for these three receptors suggests that occupancy of the D4 subclass is not mandatory for achieving antipsychotic effects, but actions at D2 or D3 receptors may be important. A major difference between typical and atypical antipsychotic drugs is in the production of extrapyramidal side effects by the typical drugs. Production of extrapyramidal side effects by typical drugs seems to be due to the use of the drugs at doses where striatal D2 receptor occupancy exceeds approximately 80\%. Use of these drugs at doses that do not produce this level of receptor blockade enables them to be used therapeutically without producing these side effects. The antipsychotic drugs have been shown to act as inverse agonists at D2 and D3 dopamine receptors, and this property may be important for the antipsychotic effects of the drugs. It is suggested that the property of inverse agonism leads to a receptor up-regulation upon prolonged treatment, and this alters the properties of dopamine synapses. Several variants of the dopamine receptors exist with different DNA sequences and in some cases different amino acid sequences. These variants may have different properties that alter the effects of dopamine and the antipsychotic drugs. The determination of such variants in patients may help in the prediction of drug responsiveness.
This article was published in Pharmacol Rev and referenced in Journal of Proteomics & Bioinformatics

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