This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone

Published online:


Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson’s disease, depression, attention deficit hyperactivity disorder, nausea and vomiting, among others. Dopamine’s actions are mediated by a family of five G-protein coupled receptors (GPCRs) (viz. D1, D2, D3, D4 and D5)1. The D2 dopamine receptor (DRD2) is the primary target for both typical2 and atypical3,4 antipsychotic drugs, and for Parkinson’s disease drugs. Unfortunately, many drugs targeting DRD2 frequently cause serious and potentially life-threatening side effects due to promiscuous activities against related receptors4,5. Accordingly, a molecular understanding of DRD2 structure and function could provide a template for the design of safer and more effective medications. Here we provide the crystal structure of DRD2 in complex with the widely prescribed atypical antipsychotic drug risperidone. The DRD2-risperidone structure reveals an unexpected mode of antipsychotic drug binding to dopamine receptors, and illuminates structural determinants essential for the actions of risperidone and related drugs at DRD2.

  • Subscribe to Nature for full access:



Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

Author information


  1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7365, USA

    • Sheng Wang
    • , Tao Che
    • , Daniel Wacker
    •  & Bryan L. Roth
  2. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158-2280, USA

    • Anat Levit
    •  & Brian K. Shoichet
  3. Division of Chemical Biology & Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360, USA

    • Bryan L. Roth
  4. National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA

    • Bryan L. Roth


  1. Search for Sheng Wang in:

  2. Search for Tao Che in:

  3. Search for Anat Levit in:

  4. Search for Brian K. Shoichet in:

  5. Search for Daniel Wacker in:

  6. Search for Bryan L. Roth in:

Corresponding authors

Correspondence to Sheng Wang or Daniel Wacker or Bryan L. Roth.

Supplementary information


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.