Reply to ‘Antipsychotics with similar association kinetics at dopamine D2 receptors differ in extrapyramidal side-effects’

David A. Sykes, J. Robert Lane, Monika Szabo, Ben Capuano, Jonathan A. Javitch, Steven J. Charlton

Research output: Contribution to journalLetterResearchpeer-review

1 Citation (Scopus)

Abstract

We thank Zeberg and Sahlholm for their correspondence regarding our recent paper proposing that drug rebinding to the dopamine D2 receptor (D2R) contributes to the extrapyramidal symptoms (EPS) observed with many antipsychotic drugs. We were gratified to note that, like us, the authors obtained a strong correlation between EPS (derived from ref. 3) and the association rates they have measured using a distinct method. We are also pleased that the new odds ratio they calculated for remoxipride fits our rebinding hypothesis, strengthening the overall correlation between EPS and kr. However, they highlight a discrepancy between the association and dissociation rates of remoxipride, which they report as being much more rapid than the values we determined. This reduces the strength of their own correlation between association rate and EPS that, they have argued, weakens our rebinding hypothesis.
Original languageEnglish
Article number3568
Number of pages5
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Sykes, David A. ; Lane, J. Robert ; Szabo, Monika ; Capuano, Ben ; Javitch, Jonathan A. ; Charlton, Steven J. / Reply to ‘Antipsychotics with similar association kinetics at dopamine D2 receptors differ in extrapyramidal side-effects’. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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abstract = "We thank Zeberg and Sahlholm for their correspondence regarding our recent paper proposing that drug rebinding to the dopamine D2 receptor (D2R) contributes to the extrapyramidal symptoms (EPS) observed with many antipsychotic drugs. We were gratified to note that, like us, the authors obtained a strong correlation between EPS (derived from ref. 3) and the association rates they have measured using a distinct method. We are also pleased that the new odds ratio they calculated for remoxipride fits our rebinding hypothesis, strengthening the overall correlation between EPS and kr. However, they highlight a discrepancy between the association and dissociation rates of remoxipride, which they report as being much more rapid than the values we determined. This reduces the strength of their own correlation between association rate and EPS that, they have argued, weakens our rebinding hypothesis.",
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Reply to ‘Antipsychotics with similar association kinetics at dopamine D2 receptors differ in extrapyramidal side-effects’. / Sykes, David A.; Lane, J. Robert; Szabo, Monika; Capuano, Ben; Javitch, Jonathan A.; Charlton, Steven J.

In: Nature Communications, Vol. 9, No. 1, 3568, 01.12.2018.

Research output: Contribution to journalLetterResearchpeer-review

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T1 - Reply to ‘Antipsychotics with similar association kinetics at dopamine D2 receptors differ in extrapyramidal side-effects’

AU - Sykes, David A.

AU - Lane, J. Robert

AU - Szabo, Monika

AU - Capuano, Ben

AU - Javitch, Jonathan A.

AU - Charlton, Steven J.

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Y1 - 2018/12/1

N2 - We thank Zeberg and Sahlholm for their correspondence regarding our recent paper proposing that drug rebinding to the dopamine D2 receptor (D2R) contributes to the extrapyramidal symptoms (EPS) observed with many antipsychotic drugs. We were gratified to note that, like us, the authors obtained a strong correlation between EPS (derived from ref. 3) and the association rates they have measured using a distinct method. We are also pleased that the new odds ratio they calculated for remoxipride fits our rebinding hypothesis, strengthening the overall correlation between EPS and kr. However, they highlight a discrepancy between the association and dissociation rates of remoxipride, which they report as being much more rapid than the values we determined. This reduces the strength of their own correlation between association rate and EPS that, they have argued, weakens our rebinding hypothesis.

AB - We thank Zeberg and Sahlholm for their correspondence regarding our recent paper proposing that drug rebinding to the dopamine D2 receptor (D2R) contributes to the extrapyramidal symptoms (EPS) observed with many antipsychotic drugs. We were gratified to note that, like us, the authors obtained a strong correlation between EPS (derived from ref. 3) and the association rates they have measured using a distinct method. We are also pleased that the new odds ratio they calculated for remoxipride fits our rebinding hypothesis, strengthening the overall correlation between EPS and kr. However, they highlight a discrepancy between the association and dissociation rates of remoxipride, which they report as being much more rapid than the values we determined. This reduces the strength of their own correlation between association rate and EPS that, they have argued, weakens our rebinding hypothesis.

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