The acute EPS of haloperidol may be unrelated to its metabolic transformation to BCPP+.

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Sikazwe DM, Li S, Lyles-Eggleston M, Ablordeppey SY

The acute EPS of haloperidol may be unrelated to its metabolic transformation to BCPP+.

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3779-82.

PubMed ID

14552778 [ View in PubMed

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Abstract

We have previously proposed that haloperidol's debilitating extrapyramidal symptoms (EPS) may be associated with its quaternary BCPP+ (an MPP+ like species) metabolite formed in vivo. However, recent work on D2 knock out mice suggests that haloperidol's EPS may be related to its potent D2 binding (K(i)=0.9 nM). In this study, we explore this question by synthesizing and testing an analogue (DS-27) that binds to D2 receptors with higher affinity than haloperidol, but cannot form quaternary metabolites. This study suggests that D2 affinity may be the primary underlying mechanism for acute catalepsy induction by haloperidol.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Clozapine	Dopamine D2 receptor	Ki (nM)	130	N/A	N/A	Details
Clozapine	Dopamine D3 receptor	Ki (nM)	240	N/A	N/A	Details
Clozapine	Dopamine D4 receptor	Ki (nM)	54	N/A	N/A	Details
Haloperidol	Dopamine D2 receptor	Ki (nM)	0.89	N/A	N/A	Details
Haloperidol	Dopamine D3 receptor	Ki (nM)	4.6	N/A	N/A	Details