# SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $385,161

## Abstract

ABSTRACT
Many clinically-used sedative and anesthetic agents act by modulating the function of the γ-aminobutyric acid
type A (GABAA) receptor. The GABAA receptor is the major inhibitory transmitter-gated ion channel in the
brain. Inhibition mediated by GABAA receptors sets the overall activity of the brain, while in individual cells it
determines the propensity of a cell to fire an action potential in response to a given excitatory input. The
GABAA receptor is also a target for numerous endogenous compounds including neuroactive steroids that can
reduce the dosage requirement for intravenous anesthetics. The overall goal of this project is to investigate
how various endogenous compounds and clinically used drugs modify the functioning of the GABAA receptor
and initiate the onset and offset of anesthesia. Specifically, we will: i) examine the interactions between binding
sites for various classes of GABAergic anesthetics; ii) test the hypothesis that modulation of tonic activity from
synaptic-type GABAA receptors contributes to the actions of anesthetics; iii) determine the effects of anesthetic
drug combinations on the function of native GABAA receptors; iv) test the hypothesis that endogenous steroids
act as co-agonists enhancing the behavioral effects of clinically used GABAergic anesthetic drugs; and v) test
the usefulness of competitive steroid-antagonists in promoting emergence from anesthesia.

## Key facts

- **NIH application ID:** 9828778
- **Project number:** 5R01GM108580-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** GUSTAV AKK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,161
- **Award type:** 5
- **Project period:** 2014-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828778

## Citation

> US National Institutes of Health, RePORTER application 9828778, SYNERGISTIC ACTIONS OF INTRAVENOUS ANESTHETICS (5R01GM108580-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828778. Licensed CC0.

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