Physical Mechanisms of Anesthesia

Roth, Sheldon H.

doi:10.1146/annurev.pa.19.040179.001111

Cited by 123 publications

(40 citation statements)

References 69 publications

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“…The role of volume property, however, is considered important in connection with this phenomenon. According to the concept of critical volume of anaesthesia (4,5), nerve conduction is blocked when drug molecules enter the lipid bilayer and causes expansion in the membrane structure to a critical volume level. The disordering of bilayer structure, resulting from volumetric expansion, causes the disfunctioning of the membrane transport property and the blockage of nerve conduction.…”

Section: Introductionmentioning

confidence: 99%

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Partial molar volumes of some drugs in water and ethanol at 35 °C

Iqbal¹,

Jamal²,

Ahmed³

et al. 1994

Can. J. Chem.

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Partial molar volumes, vO, of six drugs, mostly anaesthetics, viz., cinchocaine HCl, lidocaine HC1, mepivacaine HC1, procaine HC1, propranolol HC1, tetracaine HCI, in water and ethanol, calculated from precision densities obtained at 35OC from a vibrating tube densitometer, are reported in this work. The data represent the smaller volumes of drug molecules in ethanol than in water. Volume contribution of hydrochloride part were calculated and excluded from V O to assess the volume of free base component of the solutes. Volumes of free bases were also found smaller in ethanol, although much closer to those in water. The differences in volumes are interpreted as due to hydrophobicity of solutes. Relative hydrophobicities were estimated from volumes of transfer from aqueous to organic media. Correlation of V O with van der Waal volumes are also reported. The hydrophobicity of these compounds is proposed to play a key role in the resulting drug action. Possible mechanism of drug binding with the membrane structure is also discussed.

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Section: Introductionmentioning

confidence: 99%

“…The disordering of bilayer structure, resulting from volumetric expansion, causes the disfunctioning of the membrane transport property and the blockage of nerve conduction. An important evidence in favour of this concept is given in terms of the observed reversal of anaesthesia under applied pressure (4).…”

Section: Introductionmentioning

confidence: 99%

Partial molar volumes of some drugs in water and ethanol at 35 °C

Iqbal¹,

Jamal²,

Ahmed³

et al. 1994

Can. J. Chem.

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“…Most theories of anaesthesia have related to the hydrophobic nature of neuronal lipid membranes and have highlighted the ease with which many anaesthetics dissolve in octanol and other 'membrane-like' substances (reviewed by Seeman, 1972; Roth, 1979). However, it was recently suggested that the striking correlation between lipid solubility and anaesthetic potency might implicate hydrophobic t To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of gamma‐aminobutyric acid‐activated Cl‐ currents in cultured rat hippocampal neurones by three volatile anaesthetics.

Jones

Brooks

Harrison

1992

The Journal of Physiology

188

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SUMMARY1. The effects of the volatile anaesthetics enflurane, halothane and isoflurane on yaminobutyric acid (GABA)A receptor-mediated chloride currents were studied in cultured rat hippocampal neurones. Transient current responses were obtained by brief pressure application of GABA to the cell body of neurones under voltage clamp.2. All three anaesthetics increased the peak amplitude and duration of current responses to brief applications of GABA. These effects were fully reversible, and did not involve alterations in the reversal potential for GABA responses.3. The experimental concentrations of anaesthetics were measured directly using gas chromatography. The enhancement of GABA currents increased with increasing anaesthetic concentration. Clinically effective concentrations of anaesthetics (between 1 and 1-5 times MAC (minimum alveolar concentration) produced significant enhancement of GABA currents.4. These results demonstrate that the changes in the time course of synaptic inhibition reported in the presence of the volatile anaesthetics are likely to result from modification of the function of postsynaptic GABAA receptor-channel complexes. These findings also support the hypothesis that GABAA receptor complexes serve as common molecular target sites for a variety of structurally diverse anaesthetic molecules.

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“…(For reviews see Miller & Miller, 1975;Roth, 1979;Janoff & Miller, 1982;Franks & Lieb, 1982. ) In these theories, anaesthetics and pressure produce effects that oppose each other.…”

Section: Introductionmentioning

confidence: 99%