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Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors

Hall, David A., Strange, Philip G. (1997) Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors. British Journal of Pharmacology, 121 (4). pp. 731-736. ISSN 0007-1188. (doi:10.1038/sj.bjp.0701196) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:18092)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1038/sj.bjp.0701196

Abstract

1 The effects of a number of D-2-like dopamine receptor antagonists have been determined on forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing the human D-2short dopamine receptor (CHO-D2S cells). 2 Dopamine inhibited the effect of forskolin (as expected for a D-2 receptor). However, all of the antagonists tested, apart from UH232 and (-)-butaclamol, were able to increase cyclic AMP accumulation above the forskolin control level. (+)-Butaclamol elicited a similar stimulation of forskolin-stimulated cyclic AMP accumulation in a CHO cell line expressing human D-2long dopamine receptors whereas it exhibited no stimulating effect on forskolin-stimulated cyclic AMP accumulation in untransfected CHO-K1 cells. 3 There was a strong correlation between the EC50 values of these compounds for potentiation of cyclic AMP accumulation and their K-i values from radioligand binding experiments in CHO-D2S cells. 4 The effects of both (+)-butaclamol and dopamine in CHO-D2S cells were inhibited by pre-treatment with pertussis toxin indicating a role for Gi/Go proteins. 5 UH232 did not significantly affect forskolin-stimulated cyclic AMP accumulation but this substance was able to inhibit the effects of both dopamine and (+)-butaclamol in a concentration-dependent manner. Thus the effects of (+)-butaclamol on forskolin-stimulated cyclic AMP accumulation an mediated directly via the D-2 receptor rather than by reversal of the effects of an endogenous agonist. 6 These data suggest that the D-2 dopamine receptor antagonists tested here, many of which are used clinically as antipsychotic drugs, are in fact inverse agonists at human D-2 dopamine receptors.

Item Type: Article
DOI/Identification number: 10.1038/sj.bjp.0701196
Uncontrolled keywords: inverse agonism; dopamine receptors; antipsychotic drugs
Subjects: R Medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: M.A. Ziai
Date Deposited: 23 Jul 2009 17:37 UTC
Last Modified: 16 Nov 2021 09:56 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/18092 (The current URI for this page, for reference purposes)

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