# Stimulation of an ectopic olfactory receptor to reverse ventilatory depression induced by opioids

> **NIH NIH U18** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $242,250

## Abstract

Project Summary/Abstract
 Substance abuse disorders involving opioids have led to a dramatic increase in overdose deaths in the
last decade. Death from opioid overdose is precipitated by the effect of opioids on the central nervous system
to suppress ventilation. The standard treatment for opioid overdose is naloxone, a µ-opioid receptor
antagonist. However, naloxone is not as effective against potent opioids like fentanyl, driving the need to find
alternative treatments to counteract opioid-induced respiratory depression. The carotid body, a peripheral
chemoreceptor that senses decreases in oxygen to increase breathing, has been the target of several drugs
(doxapram, almitrine, and GAL-021) that stimulate ventilation. Interestingly, these drugs can be effective in
reversing opioid-induced respiratory depression, but their use is limited by significant side effects. We propose
to test the potential of targeting the carotid body through an ectopic olfactory receptor Olfr78 to counteract
ventilatory depression caused by opioids. Olfr78 is expressed highly in the carotid body and mediates sensory
signaling. To test the therapeutic potential of this approach, we propose the following aims. First, we will
determine the ability of existing Olfr78 agonists to stimulate ventilation and reverse respiratory depression
induced by morphine and fentanyl. Next, we will perform a high throughput small molecule screen to identify
more potent and specific agonists of Olfr78 and verify their ability to acutely activate Olfr78. Finally, we will test
the best Olfr78 agonists from the screen for their ability to stimulate carotid body sensory activity as well as
ventilation to counteract opioid-induced respiratory depression.

## Key facts

- **NIH application ID:** 10107135
- **Project number:** 1U18DA052505-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Andy J. Chang
- **Activity code:** U18 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $242,250
- **Award type:** 1
- **Project period:** 2020-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107135

## Citation

> US National Institutes of Health, RePORTER application 10107135, Stimulation of an ectopic olfactory receptor to reverse ventilatory depression induced by opioids (1U18DA052505-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10107135. Licensed CC0.

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