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Related Experiment Videos

Halogenation and anesthetic potency.

A G Targ1, N Yasuda, E I Eger

  • 1Department of Anesthesia, University of California, San Francisco 94143-0464.

Anesthesia and Analgesia
|May 1, 1989
PubMed
Summary

New ether anesthetics demonstrate that increasing halogen size enhances potency and lipid solubility. The product of anesthetic potency and lipid solubility remains constant, challenging narcosis theories.

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Area of Science:

  • Anesthesiology
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Anesthetic potency correlates with halogen size, but previous studies lacked accuracy and scope.
  • Ether anesthetics are understudied regarding structure-activity relationships.

Purpose of the Study:

  • To investigate the anesthetic properties of I-537 and compare it with other ether anesthetics.
  • To establish relationships between the structure of ether anesthetics and their activity.
  • To explore the implications for the unitary theory of narcosis.

Main Methods:

  • Determined the oil/gas partition coefficient and Minimum Alveolar Concentration (MAC) for I-537.
  • Compared I-537 with I-653 and isoflurane, varying the 1-ethyl halogen (F, Cl, Br).

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Main Results:

  • I-537 has an oil/gas partition coefficient of 245 and a MAC of 0.52% in rats.
  • Increasing halogen atomic weight (F < Cl < Br) decreased MAC (increased potency) and increased lipid solubility.
  • The product of MAC and oil/gas partition coefficient was constant (120 +/- 11) for these ethers.

Conclusions:

  • Anesthetic potency and lipid solubility of ether anesthetics increase with halogen atomic weight.
  • The constant product of MAC and lipid solubility challenges the unitary theory of narcosis or the suitability of olive oil as a model.
  • Further research is needed to understand the mechanism of anesthetic action.