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Updated: Jun 23, 2026
08:49
Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Isovaleric, methylmalonic, and propionic acid decrease anesthetic EC50 in tadpoles, modulate glycine receptor
Yun Weng1, Tienyi Theresa Hsu, Jing Zhao
1Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143-0464, USA.
Anesthesia and Analgesia
|April 18, 2009
Summary
Isovaleric acid (IVA), methylmalonic acid (MMA), and propionic acid exhibit anesthetic properties. These organic acids enhance glycine receptor activity and alter lipid membrane properties, potentially explaining central nervous system depression in organic acidemias.
Area of Science:
- Neuroscience
- Biochemistry
- Anesthesiology
Background:
- Elevated isovaleric (IVA), methylmalonic (MMA), and propionic acid concentrations are linked to impaired consciousness in genetic organic acidemias.
- These metabolites may possess anesthetic properties contributing to central nervous system depression in these disorders.
Purpose of the Study:
- To investigate the potential anesthetic effects of IVA, MMA, and propionic acid.
- To determine if these organic acids modulate glycine and GABA(A) receptor function.
- To assess the impact of these compounds on lipid physical properties.
Main Methods:
- Anesthetic effective concentration 50% (EC50) determination in Xenopus laevis tadpoles.
- Two-electrode voltage clamp analysis of expressed glycine and GABA(A) receptors in Xenopus oocytes.
- Measurement of lipid monolayer pressure-area isotherms using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC).
Main Results:
- Isovaleric acid demonstrated anesthetic effects in tadpoles; MMA and propionic acid halved isoflurane's EC50.
- All three organic acids increased glycine receptor currents concentration-dependently, with minimal impact on GABA(A) receptors.
- The organic acids increased the lateral pressure of DPPC lipid monolayers.
Conclusions:
- IVA, MMA, and propionic acid possess anesthetic properties in tadpoles.
- These organic acids positively modulate glycine receptor function.
- The compounds affect the physical properties of DPPC lipid monolayers.
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