Corey Hopkins
University of Nebraska Medical Center, NE·Pharmacology
Two of the most-used drug classes in neurology and pain medicine come with limits that patients feel directly: opioids can cause addiction and dangerous slowing of breathing, and the main Parkinson's drug eventually triggers uncontrolled involuntary movements. Both projects here take a chemistry route to the problem, designing and steadily refining small drug-like molecules that act on newly identified protein targets, then testing them in animal models of pain and of movement side effects.
- Fields
Pharmacology
Chemistry
Neuroscience
- Topics
medicinal chemistry
GIRK channels
potassium channels
- Grants
- 2 known grants, through Mar 2028
What they work on
- Optimize the lead chemical scaffold of GIRK1/2 activators, molecules that open potassium channels which quiet nerve cells, for potency, selectivity over related channels, and favorable absorption and clearance properties.
- Build a dose-to-effect relationship for GIRK1/2 activators using a carrageenan-induced inflammatory pain model in mice, so that compounds meeting the exposure and efficacy criteria can be advanced into chronic pain models.
- Test whether GIRK1/2 activators relieve pain alone and enhance morphine's effect without causing motor impairment or reward-like behavior, assessed in mouse acute and persistent pain models and the conditioned place preference assay.
- Improve the metabolic stability of three chemical scaffolds that block the dopamine D4 receptor while preserving their potency and selectivity over other dopamine receptor subtypes, using paired medicinal chemistry and drug-metabolism studies.
- Evaluate the optimized D4 receptor antagonists in an animal model of L-DOPA-induced dyskinesias, the involuntary movements that limit long-term use of the main Parkinson's disease drug.
More about the research
The shared method is iterative medicinal chemistry: make a batch of related compounds, measure how potently and selectively they hit the target and how the body absorbs and clears them, and feed those results into the next round of design.
Why it matters
Chronic pain is widespread and often poorly controlled, and the current mainstays carry addiction and respiratory risks; a non-opioid compound that opens GIRK channels could offer pain relief, or allow lower opioid doses, without those liabilities. Separately, roughly 10% of Parkinson's patients per year develop L-DOPA-induced dyskinesias within the first several years of treatment and no therapy prevents or reverses them, so a selective D4 blocker could address an unmet need.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thomas Keck
Rowan University, NJ·Pharmacology
Test whether combining morphine with MP-III-024, a compound that enhances α2/α3 GABA-A receptor signaling, gives stronger pain relief without more tolerance, constipation or respiratory depression in preclinical models.
Alexandra Nelson
University of California-San Francisco, CA·Neuroscience
Test whether local inhibitory synapses within the striatum, and inhibitory inputs from the globus pallidus, are altered in and contribute to levodopa-induced dyskinesia, using in vivo and ex vivo electrophysiology, optogenetics, and chemogenetics in parkinsonian mice.
Naoto Hoshi
University of California-Irvine, CA·Pharmacology
Identify potent compounds that stabilize the binding of Kv7 potassium channels to PIP2, a membrane lipid the channel needs, using a newly developed in silico (computer-based) screening process.
The school
University of Nebraska Medical Center: 20 labs on PI Pages, $657M a year on research, 82 research doctorates a year.
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