The membrane concentrations of neutral and positive anesthetics (alcohols, chloropromazine, morphine) fit the meyer-overton rule of anesthesia; negative narcotics do not

Roth, Sheldon H.; Seeman, Philip

doi:10.1016/0005-2736(72)90023-5

Cited by 146 publications

(57 citation statements)

References 22 publications

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“…A possible explanation is that the more fluid structure of the highly curved monolamellar vesicles (diameters in the range of Johnson, 1973) provides a better solvent for the barbiturate because less work has to be done to introduce the barbiturate between the lipid molecules. The finding that the partition coefficient is independent of pentobarbitone concentration ( Figure 1) is consistent with that obtained by Roth & Seeman (1972) in erythrocyte ghosts. This implies either that there are no free discrete binding sites at these concentrations (i.e.…”

Section: Discussionsupporting

confidence: 90%

THE DEPENDENCE OF THE LIPID BILAYER MEMBRANE: BUFFER PARTITION COEFFICIENT OF PENTOBARBITONE ON pH AND LIPID COMPOSITION

Miller

1977

British J Pharmacology

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The membrane/buffer partition coefficient of [14C]‐pentobarbitone has been determined as a function of the lipid composition of bilayer membranes. A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilibration. The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studied. The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbitone. Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former. At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes. Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient. High pressures do not greatly change these partition coefficients.

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Section: Discussionsupporting

confidence: 90%

THE DEPENDENCE OF THE LIPID BILAYER MEMBRANE: BUFFER PARTITION COEFFICIENT OF PENTOBARBITONE ON pH AND LIPID COMPOSITION

Miller

1977

British J Pharmacology

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“…The concentration of alcohol needed to produce a given reduction in ti,2 decreased dramatically with increasing chain length, and the relationship between BN and carbon chain length N was exponential (Figure 3). Since the relationship between membrane/buffer partition coefficients and N is also exponential (Roth & Seeman, 1972), this suggests that the effectiveness of an alcohol may be directly related to its concentration in the lipid phase of the membrane (Gage et al, 1975).…”

Section: Resultsmentioning

confidence: 99%

“…The relationship between carbon chain length and alcohol potency, determined from the slope of dose-response curves, is exponential. Membrane/ buffer partition coefficients are also exponentially related to carbon chain length (Roth & Seeman, 1972), implying that the potency of an alcohol is directly related to its partition coefficient.…”

Section: Ethanol Does Not Alter Voltage Sensitivitymentioning

confidence: 99%

Aliphatic alcohols increase the decay rate of glutamate‐activated currents at the crayfish neuromuscular junction

Wachtel

1984

British J Pharmacology

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1Excitatory junction currents produced by glutamate were recorded with an extracellular electrode at the excitatory neuromuscular junction of the crayfish. 2 The currents decayed more quickly as the membrane was hyperpolarized. The direction of the voltage sensitivity of the decay phase is thus opposite to that found for acetylcholine-activated currents at the amphibian endplate. 3 The aliphatic alcohols ethanol to octanol all increased the rate of decay of the currents. The effects of the short chain alcohols were opposite to their actions at the toad endplate, where ethanol to pentanol prolong the currents. This observation was explained in terms of the opposite direction of the voltage sensitivity in the two preparations.4 For each alcohol, the relationship between the half-decay time of the currents (t1/2) and alcohol concentration was exponential. 5 The potency of each alcohol in decreasing tr12 was exponentially related to carbon chain length, which would be predicted if the effects of the alcohols were directly related to their concentration in the lipid phase of the membrane. 6 These findings are consistent with the ideas that the alcohols may alter membrane polarizability or change membrane fluidity in the vicinity of the channels.

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“…(Nerve data for H(CH 2)n0H 3.0r The effects of various agents on the stability of the Nerve Dose erythrocyte membrane have been extensively studied FIGURE 3. Correlation between hemolytic activity and loss of nerve (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Hemolysis has been shown to correlate well with excitability induced by primary alcohols (n = 1 -9).…”

Section: Methodsmentioning

confidence: 99%

“…The relationship has been used to explain the potency of local anesthetics (4), general anesthetics (5), and tranquilizers and central nervous system depressants (6). The Meyer-Overton rule does not explain how the drug's lipid solubility leads to a disruption of membrane excitability, but many experimental observations are consistent with this view (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

Anderson¹,

Glasgow²,

Dunham³

1984

Environ Health Perspect

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The expense, length of time and number of animals required for routine toxicity testing have provided the incentive for finding alternative techniques which are faster, less expensive and equally valid. The purpose of this work was to examine the value of a simple in vitro test (hemolysis) as a correlate of the neurotoxicity produced by commonly used industrial organic solvents. Incubation of rat erythrocytes with organic alcohols produced hemolysis which correlates with the potency of the same alcohols to suppress membrane excitability, measured as reduction in the evoked action potential of the rat sciatic nerve. The hemolytic activity also reflects changes in water solubility among the compounds and thus can be used as an index of in vivo neurotoxicity, the extent of which partly depends on absorption of the agent and delivery to nerve tissue. Hemolysis therefore may be of value as a preliminary test for assessing the neurotoxicity of organic solvents.

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The membrane concentrations of neutral and positive anesthetics (alcohols, chloropromazine, morphine) fit the meyer-overton rule of anesthesia; negative narcotics do not

Cited by 146 publications

References 22 publications

THE DEPENDENCE OF THE LIPID BILAYER MEMBRANE: BUFFER PARTITION COEFFICIENT OF PENTOBARBITONE ON pH AND LIPID COMPOSITION

THE DEPENDENCE OF THE LIPID BILAYER MEMBRANE: BUFFER PARTITION COEFFICIENT OF PENTOBARBITONE ON pH AND LIPID COMPOSITION

Aliphatic alcohols increase the decay rate of glutamate‐activated currents at the crayfish neuromuscular junction

Hemolysis as a possible indicator of neurotoxicity induced by organic solvents.

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