Methods of Making and Using Dopamine D3 Receptor Selective Antagonists/Partial Agonists

Dopamine is a major neurotransmitter in the central nervous system and among other functions is directly related to the rewarding effects of drugs of abuse. Dopamine signaling is mediated by D1, D2, D3, D4 and D5 receptors. The dopamine D3 receptor is a known target to treat a variety of neuropsychiatric disorders, including substance use disorders (e.g., cocaine and opioid), schizophrenia and depression. Despite extensive efforts, it has proven difficult to identify a lead molecule that selectively binds to D3 receptors (versus D2 receptors, for example), with the desired pharmacological and pharmacokinetic profile. For example, metabolic instability or predicted toxicity has precluded successful translation of previously reported D3 R-selective antagonists to clinical use for cocaine abuse.

A library of novel compounds has been designed to have high affinity and specificity for the dopamine D3 receptor. Preliminary studies at the National Institute of Drug Abuse (NIDA) indicate that selected lead compounds have promising in vivo activity in rodents, including reduced acquisition to self-administration of oxycodone, inhibition of reinstatement to oxycodone seeking, and ameliorating naloxone-precipitated withdrawal from oxycodone dependence.

Potential Commercial Applications: Competitive Advantages:
  • Treatment of opioid use disorders
  • Treatment of schizophrenia
  • Treatment of bipolar disorder
  • Treatment of cannabis (Tetrahydrocannabinol, THC) dependence
  • Despite extensive efforts to develop D3 receptor-selective compounds, it has proven difficult to identify a ligand with the desired pharmacological and pharmacokinetic profile for translation to the clinic. The D3 receptor ligands described herein may be useful to treat a variety of diseases, including opioid use disorders and schizophrenia.


Amy Newman (NIDA)  ➽ more inventions...

Vivek Kumar (NIDA)  ➽ more inventions...

Intellectual Property:
US Application No. 62/307,600
PCT Application No. PCT/US2017/021328

Kumar V, et al. PMID 27508895

Collaboration Opportunity:

Researchers at the NIDA seek licensing and/or co-development research collaborations for development of Dopamine D3 ligands to treat opioid use disorders. Requests for copies of the patent application or inquiries about licensing, research collaborations, and co-development opportunities should be sent to Martha Lubet, Ph.D. at

Licensing Contact:
Martha Lubet, Ph.D.
Phone: 240-276-5508

OTT Reference No: E-053-2016/0
Updated: Mar 8, 2017