TIPS - September 1988 IVol. 91

can also be obtained with perfectly sound data2. What is usually wrong is the interpretation of these data. Consider, as an exam- ple, the following ligand-receptor system:

where R is receptor, L is labelled ligand and I is inhibitor; k, Kd and Ki are the respective dissociation constants.

Algebraic manipulation of the relevant equilibrium and mass conservation expressions leads to the foltowing equation:

wLla% - B) = (1 + [I]/&) a

x m+ 2Kd (B/F)

with B = &I_.] (bound labelled ligand) and F = [LJ (free labelled ligand).

This ligand-receptor system is fully reversible but results in non- !inear Scatchard plots (Fig, la). The curved lines do, of course, intersect at B,, (B/F = 0 => B = B,,). The experimenter, however, when coming across such a system, is only able to determine some points of the curves. Non-linearity of the system may not be seen as it is not usually possible to go to the high values of labelled ligand required to come near to the intersection of the curves with B,, (Fig. lb). Thus the experimenter determines the apparently linear beginning of the curves only, and therefore does what is shown in Fig. lc, i.e. assumes that the rest of the curves are linear too. The result is an apparent reduction in B,,, and apparent non-competitive in- hibition. The point is: there is nothing artefactual about the ex- perimentally determined data, it is their interpretation that is wrong.

HUBERT REHM AND

CORD-MICHAEL BECKER*

Centre de Biochimie, Universitt de Nice, Part Vulrose. 06034 Nice Cedex. France. *Zentrum fiir Moiekulare Biologic, lkiuersitiit Heidel- berg, Im Neuenheimer Fefd 282, D-6900, Heidelberg, FRG.

References 1 Tomlinson, G. (1988) Trends Dharmacol.

Sci. 9, 159-162 2 Schmidt. R. R.. Eeiz, ii. and Rehm, H.

(1988) Bkchemkty 2?, 963-967

replies: Drs Rehm and Becker have pro- vided another good example of how the appearance of non-com- petitive inhibition might arise. The ‘artefact’ in question* is cre- ated the moment the investigator chooses b draw Scatchard plots that cut the abscissa at some point below the true B,,, +ity of experimental data notwithstand- ing. It is in this sense that I used the term in my article and the two- receptor example I described would

317

generate Scatchard plots similar to those shown by Drs Rehm and Becker. Thus, they and.1 are in full agreement.

GBORGE TOMLINSON

Department of Pharmacology and Therapeu- tics, University of Munitoba, Faculty of Medi- ctne, 770 Bannatyne Avenue, Winnipeg, Man- itoba R3E OWS, Canada und Department of Chemistry, University of Winnipeg.

*artefact: a product of artificial character due to extraneous (as human) agency. Webster’s Third international Dictionary)

The acceptable face of international competition

Stereophobia: ht In their recent TiPS leader article’ ‘Racemates: iowards a new year

tageous in countries persistently

resolution’, R. L. Smith and J. loyal to racemic mixtures e.g. the

Caldwell state: ‘In Japan, the health European countries and the USA.

authorities, in meetings with the A similar situation is expected to

pharmaceutical industry, have ex- arise for racemic pesticides versus

plained their requirements in the single isomeric products free of the

context of the registration of a 50% ballast which serves only as expensive (double costs of basic

racemic mixture or optical isomer. chemicals, double loads in trans- Basically, for a racemic mixture, information will be required on the

port and application) environ-

toxicity pharmacology (efficacy and mental pollutant.

This is not only a fair, but also a general) and the disposition of each conscientious form of international isomer. Also when the active com- competition. Pharmaceutical in- ponent is either of the two isomers, dustrles should accept this and rid information will be required on the themselves of their ‘stereophnbia’. extent of interconversion of the two isomeric forms.’ The latter is an E. J.ARIiiNS

aspect of the pharmacokinetics of Institute of Pharmacology and Toxicology, single isomeric products. University of Nijmegen, Ceert Crootepleia

This implies that racemates will N22, PO Box 9201, 6500 HB Nijmegen, The

have a hard time penetrating the Netherlands.

Japanese market and that single Reference isomer products, free of high-risk 1 Smith, R. L.‘and Caldwell, J. (1988) Trends isomeric ‘ballast’, will be advan- Pharmacol. Sci. 9, 7577

Full colour reprints of the centrefold published in this issue of TiPS, and in earlier issues are available:

hice per 5 copies is S.90 or US$9.00 (incl. p, & p.). Larger orders (lOO+) available at 15% discount.