Overton rule

It thus follows that the membrane concentration of typical P-gp substrates for halfmaximum activation of P-gp falls in the range of 1 to 10 mmole drug per mole lipid. This is a much narrower concentration range than that required for the same substances in the aqueous phase 10 8 to 10 3 M. A similar phenomenon has been observed in anesthesia. The membrane concentration of anesthetics required for anesthesia has been found to be 33 mM, independent of the anesthetic applied (Meyer-Overton rule). 

E) Enantiomers of inhalational agents provide support for the Meyer Overton rule. 

General anesthetics are soluble in lipids. Only a few are soluble in water. Furthermore, there is a well known correlation between anesthetic potency and lipid solubility. It is the Meyer-Overton rule that has been known for 80 years to researchers in anesthesia.. This relationship was thoroughly studied and reexamined in recent years (See ). In its most modem form the lipid solubility or oil/water partition coefTicient is plotted against the so-called righting reflex taken for a measure of anesthetic potency. It is log 1/p where p is the effective anesthetic pressure in atmospheres required to suppress the righting reflex of mice in half of the experimental animals On this relationship arc based the unitary hypothesis and the hydrophobic site theory which state that all general anesthetics act by the same mechanism at the same molecular or sub-cellular sites of the membrane and that the sites are hydrophobic. 

Bovill J G 2000 Mechanisms of anaesthesia time to say farewell to the Meyer-Overton rule. Current Opinion in Anaesthesiology 13 433-436 Carter A J 1999 Dwale an anaesthetic from old England. British Medical Journal 319 1623-1626 (use of medicinal herbs to render a patient unconscious for surgery, before modem general anaesthesia)... 

Cantor, R. S. (2001). Breaking the Meyer-Overton rule Predicted effects of varying stiffness and interfecial activity on the intrinsic potency of anesthetics. Biophysical Journal, 80 ), 2284-2297. 

One effect of mechanical anharmonicity is to modify the Au = t infrared and Raman selection rule to Au = 1, 2, 3,. .., but the overtone transitions with Au = 2, 3,... are usually weak compared with those with Au = t. Since electrical anharmonicity also has this effect both types of anharmonicity may contribute to overtone intensities. 

It follows from Equation (6.58) that the 1q, 2q and 3q transitions of H2O are allowed since Vj, V2 and V3 are Ui, and 2 vibrations, respectively, as Equation (4.11) shows. We had derived this result previously simply by observing that all three vibrations involve a changing dipole moment, but the rules of Equation (6.57) enable us to derive selection rules for overtone and combination transitions as well. 

Raman spectroscopy can in principle be applied to this problem in much the same manner as infrared spectroscopy. The primary difference is that the selection rules are not the same as for the infrared. In a number of molecules, frequencies have been assigned to combinations or overtones of the fundamental frequency of the... 

Pohl, P. A new model of weak add permeation through membranes revisited does Overton still rule Biophys. J. 2006, 90, L86-88. 

In a case where the transition of an energy state is from 0 to 1 in any one of the vibrational states (vi,v2,v3,. ..), the transition is considered as fundamental and is allowed by selection rules. When a transition is from the ground state to v — 2,3,. .., and all others are zero, it is known as an overtone. Transitions from the ground state to a state for which Vj = 1 and vj = 1 simultaneously are known as combination bands. Other combinations, such as v — 1, Vj = 1, v = 1, or v, — 2, v7 — 1, etc., are also possible. In the strictest form, overtones and combinations are not allowed, however they do appear (weaker than fundamentals) due to anharmonicity or Fermi resonance. 

When the potential is of the Morse type, the first term in Eq. (2.80) provides an often-used rule of thumb for overtone (v — v > 1) transitions... 

The Meyer-Overton hypothesis proposed that once a sufficient number of anaesthetic molecules were dissolved in the lipid membranes of cells within the central nervous system, anaesthesia would result by a mechanism of membrane disruption. While an interesting observation, there are several exceptions to the rule that make it insufficient to account fully for the mechanism of anaesthesia. 

There are two effects of the anharmonicity of the quantized energy levels described above, which have signiflcance for NIRS. First, the gap between adjacent energy levels is no longer constant, as it was in the simple harmonic case. The energy levels converge as n increases. Second, the rigorous selection rule that An = +1 is relaxed, so that weak absorptions can occur with n = 2 (flrst overtone band), or +3 (second overtone band), etc. 

So far the effect of anharmonicity in determining the frequency of overtone (An >1) absorptions, and its effect in relaxing quantum selection rules to allow these transitions to have some absorption intensity have been considered. 

When exposed to electromagnetic radiation of the appropriate energy, typically in the infrared, a molecule can interact with the radiation and absorb it, exciting the molecule into the next higher vibrational energy level. For the ideal harmonic oscillator, the selection rules are Av = +1 that is, the vibrational energy can only change by one quantum at a time. However, for anharmonic oscillators, weaker overtone transitions due to Av = +2, + 3, etc. may also be observed because of their nonideal behavior. For polyatomic molecules with more than one fundamental vibration, e.g., as seen in Fig. 3.1a for the water molecule, both overtones and... 

An additional point that should be considered is that in the harmonic oscillator approximation, the selection mle for transitions between vibrational states is Ay = 1, where v is the vibrational quantum number and Ay > 1, that is, overtone transitions, which involve a larger vibrational quantum number change, are forbidden in this approximation. However, in real molecules, this rule is slightly relaxed due to the effect of anharmonicity of the oscillator wavefunction (mechanical anharmonicity) and/or the nonlinearity of the dipole moment function (electrical anharmonicity) [55], affording excitation of vibrational states with Ay > 1. However, the absorption cross sections for overtone transitions are considerably smaller than for Ay = 1 transitions and sharply decrease with increasing change in Av. 

A rule of thumb for hydride stretches [56, 57] is that the intensities of the vibrational overtone and combination transitions decrease, approximately, as IQ-Ay jjjg drop-off in intensity for the first few quanta of excitation may be even steeper, by another factor of 10. This implies that, in a specific spectral interval, the strongest vibrational transitions from the vibrationless ground state level correspond to the transition with the smallest Av and the greatest anharmonicity. However, as shown later, even these small absorption cross sections of vibrational overtone transitions can be sufficient for overtone preexcitation. 

Anharmonicity leads to deviations of two kinds. At higher quantum numbers, AE becomes smaller, and the selection rule is not rigorously followed as a result, transitions of A 2 or 3 are observed. Such transformations are responsible for the appearance of overtone lines at frequencies approximately two or three times that of the fundamental line the intensity of overtone absorption is frequently low, and the peaks may not be observed. Vibrational spectra are further comphcated by the fact that two different vibrations in a molecule can interact to give absorption peaks with frequencies that are approximately the sums or differences of their fundamental frequencies. Again, the intensities of combination and difference peaks are generally low. 

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