Source 1primary paper2023Neuron
Toolkit/PhOX
PhOX
Also known as: photoactivatable oxymorphone
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
we developed photoactivatable oxymorphone (PhOX)
Usefulness & Problems
Why this is useful
PhOX is a photoactivatable oxymorphone variant used for light-triggered opioid agonism in the brain after systemic delivery in an inactive form. The abstract reports that its photoactivation changes local receptor occupancy, neural activity, neurochemical signaling, and behavior.; local light-triggered activation of an opioid agonist in vivo; bidirectional manipulation of endogenous opioid receptors when paired with a photoactivatable antagonist; studying neural and behavioral effects of opioid receptor activation with optical timing control
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PhOX is a photoactivatable oxymorphone variant used for light-triggered opioid agonism in the brain after systemic delivery in an inactive form. The abstract reports that its photoactivation changes local receptor occupancy, neural activity, neurochemical signaling, and behavior.
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local light-triggered activation of an opioid agonist in vivo
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bidirectional manipulation of endogenous opioid receptors when paired with a photoactivatable antagonist
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studying neural and behavioral effects of opioid receptor activation with optical timing control
Problem solved
It addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.; reduces reliance on slow and invasive site-specific drug delivery in the brain; enables systemic administration followed by local activation in the brain
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It addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.
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reduces reliance on slow and invasive site-specific drug delivery in the brain
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enables systemic administration followed by local activation in the brain
Problem links
enables systemic administration followed by local activation in the brain
LiteratureIt addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.
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It addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.
reduces reliance on slow and invasive site-specific drug delivery in the brain
LiteratureIt addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.
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It addresses the difficulty of slow, invasive, site-specific drug delivery in the brain by allowing local activation with light after systemic dosing.
Published Workflows
Objective: Enable site-specific, bidirectional manipulation of endogenous opioid receptors in vivo using systemically delivered inactive drugs that can be locally activated in the brain with light, while supporting neural and behavioral measurements.
Why it works: The abstract states that inactive caged opioid drugs can be administered systemically and then activated locally in the brain with light, which is presented as a way to achieve site-specific control while interfacing with neural recordings.
light-triggered activation of inactive opioid ligands in the brainagonist and antagonist control of endogenous opioid receptorssystemic administration of inactive caged drugslocal photoactivation in vivooptical recording of extracellular dopamine
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
No technique tags yet.
Target processes
recombinationsignalingInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: sensor
Use requires systemic administration of the inactive compound and optical illumination of brain regions to activate it. The paper also describes combining it with optical recording of extracellular dopamine.; requires light delivery to the brain for activation; requires systemic administration in an inactive form
The abstract does not show that PhOX eliminates all delivery or specificity challenges, and it does not provide detailed limits on pharmacokinetics or off-target effects.; abstract only supports in vivo use after light delivery and does not specify synthesis, kinetics, or off-target limits
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in opioid sensitivity of mesolimbic dopamine circuitry after chronic morphine administration.
Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in the opioid sensitivity of mesolimbic dopamine circuitry in response to chronic morphine administration.
In vivo photopharmacology with caged opioid drugs is feasible and offers experimental advantages for brain studies.
we demonstrate the feasibility and experimental advantages of in vivo photopharmacology using "caged" opioid drugs
Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and pain- and reward-related behaviors.
Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and multiple pain- and reward-related behaviors.
This work establishes a general experimental framework for using in vivo photopharmacology to study the neural basis of drug action.
This work establishes a general experimental framework for using in vivo photopharmacology to study the neural basis of drug action.
The authors developed PhOX and PhNX as photoactivatable variants of oxymorphone and naloxone to enable bidirectional manipulation of endogenous opioid receptors in vivo.
To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX)
Approval Evidence
1 source3 linked approval claimsfirst-pass slug phox
we developed photoactivatable oxymorphone (PhOX)
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applicationsupports
Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in opioid sensitivity of mesolimbic dopamine circuitry after chronic morphine administration.
Combining PhOX photoactivation with optical recording of extracellular dopamine revealed adaptations in the opioid sensitivity of mesolimbic dopamine circuitry in response to chronic morphine administration.
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functional effectsupports
Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and pain- and reward-related behaviors.
Photoactivation of PhOX in multiple brain areas produced local changes in receptor occupancy, brain metabolic activity, neuronal calcium activity, neurochemical signaling, and multiple pain- and reward-related behaviors.
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tool developmentsupports
The authors developed PhOX and PhNX as photoactivatable variants of oxymorphone and naloxone to enable bidirectional manipulation of endogenous opioid receptors in vivo.
To enable bidirectional manipulations of endogenous opioid receptors in vivo, we developed photoactivatable oxymorphone (PhOX) and photoactivatable naloxone (PhNX)
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Comparisons
Source-stated alternatives
The abstract contrasts this approach with traditional site-specific drug delivery methods in the brain. It also presents PhNX as a complementary photoactivatable antagonist for bidirectional control.
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The abstract contrasts this approach with traditional site-specific drug delivery methods in the brain. It also presents PhNX as a complementary photoactivatable antagonist for bidirectional control.
Source-backed strengths
inactive before light activation after systemic administration; produced local changes across receptor occupancy, metabolic, neural, neurochemical, and behavioral readouts; can be combined with optical dopamine recording
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inactive before light activation after systemic administration
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produced local changes across receptor occupancy, metabolic, neural, neurochemical, and behavioral readouts
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can be combined with optical dopamine recording
Compared with PhNX
The abstract contrasts this approach with traditional site-specific drug delivery methods in the brain. It also presents PhNX as a complementary photoactivatable antagonist for bidirectional control.
Shared frame: source-stated alternative in extracted literature
Strengths here: inactive before light activation after systemic administration; produced local changes across receptor occupancy, metabolic, neural, neurochemical, and behavioral readouts; can be combined with optical dopamine recording.
Relative tradeoffs: abstract only supports in vivo use after light delivery and does not specify synthesis, kinetics, or off-target limits.
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The abstract contrasts this approach with traditional site-specific drug delivery methods in the brain. It also presents PhNX as a complementary photoactivatable antagonist for bidirectional control.
Ranked Citations
- 1.