Null Methods

Ehlert, F. J. (1988). Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods. Mol. Pharmacol. 33 187-194. 

Null method, physiological or pharmacological effects are translations of biochemical events by the cell. The null method assumes that equal responses emanate from equal initial stimulation of the receptor therefore, when comparing equal responses, the complex translation is cancelled and statements about the receptor activity of agonists can be made. Relative potencies of agonists producing equal responses thus are interpreted to be measures of the relative receptor stimuli produced by the agonists at the receptor see Chapter 5.6.2. 

The use of the Schild method for estimation of the dissociation equilibrium constant of a competitive antagonist is described in detail in Chapter 1. The great advantage of the Schild method lies in the fact that it is a null method agonist occupancy in the absence or presence of antagonist is assumed to be equal when responses in the absence or presence of the antagonist are equal. Even when the relationship between occupancy and response is complex, the Schild method has been found to work well. 

Delbriick et al., (1976) have recently sought to determine whether or not the stimulation of Phycomyces involves the excitation of the lowest triplet state of riboflavin. They determined an action spectrum of light-growth response between 575 and 630 nm using a tunable laser beam and taking advantage of the null method described above. This action spectrum was compared with an action spectrum obtained by computer extrapolation of a phototropic action spectrum covering 445—560 nm. 

Phase changes as small as 2 tr x 10 rad have been detected 269) by using a null method where phase drifts of the apparatus are compensated by a calibrated and controllable dielectric in cavity B. The response time of this laser interferometer is less than 5 psec when operated at 3.39 pm and repetitively pulsed plasmas can therefore be investigated. Gerardo etal. 270) even reached a time resolution of... 

The influence of major variables indicated above on the electrokinetic potential and degree of hydration of AS, BAS and BAC hydrolysis product particles has been studied in detail. The electrophoretic mobility of particles was measured by microelectrophoresis. As a measure of hydration of HPP the time of spin-spin relaxation of protons of adsorbed/adherent water (7j) was used. The 7j values were measured by NMR with a pulse relaxometer by the null method.5 The results obtained can be summarised as follows. 

The experiments about to be described were, therefore, undertaken in order to test this prediction in the case of palladium-hydrogen since the earlier observations, having been made by null methods, gave only the resistance for zero current. ... 

An important and precise traditional method of measuring capacitance for dipole moment determinations is the heterodyne beat method, a particular form of the null method mentioned above. The output of an LC oscillator incorporating the capacitance... 

A variant, proposed by Nunn and Everett ), and briefly called the null-method keeps the initial composition X2(i) constant by adding 2 to the system when this component adsorbs. The amount added is Just the surface excess. The advantage is that the original amount n2(i) need not be known. This variant may also be combined with the circulation method. 

Absorbance may be derived from the photoelectric signal either directly on a precalibrated meter scale or by a null method where a reference signal is provided optically or electrically. In null methods, readings... 

Since the method requires no deflection of the galvanometer it is known as the null method. 

A remaining question is the performance of the B-null and PW-null methods, which performed well (recall that B-null also gave good results for the first two reactions). In the case of H3, direct examination of the features of the potential surfaces [73] reveals that the agreement with experiment is indeed fortuitous, and so this is most likely the case with the previous reactions as well. 

---