Centre Modelling

As shown in Section II.E, such through-bond interactions can be explained on the basis of a simple three-centre model involving the two interacting jr-MOs and the intervening cr-MO. Of course, such models can also be applied to the changes in Ecr upon ionization, but all that can be learned from them in this context is that B = (jra H jrb increases. If... 

Copper enzymes are involved in reactions with a large number of other, mostly inorganic substrates. In addition to its role in oxygen and superoxide activation described above, copper is also involved in enzymes that activate methane, nitrite and nitrous oxide. The structure of particulate methane mono-oxygenase from the methanotrophic bacteria Methylococcus capsulatus has been determined at a resolution of 2.8 A. It is a trimer with an a3P33 polypeptide arrangement. Two metal centres, modelled as mononuclear and dinuclear copper, are located in the soluble part of each P-subunit, which resembles CcOx subunit II. A third metal centre, occupied by Zn in the crystal, is located within the membrane. 

The two models chosen by USNA team are clearly outliers from the family of available models. The Canadian Climate Centre model (acronymed by the USNA as CGCM1) is one of the very few that produces a substantially exponential (rather than linear) change in temperature. The other model used by the team is known as the Hadley Centre Model (acronymed by the USNA as HadCM2), developed at the United Kingdom s Meteorological Office.6... 

In addition to the VSEPR theory8 mentioned above, other theoretical or semiempirical approaches have addressed the problem of the positions occupied by various ligands as a function of their nature, for comparison with the numerous experimental results now available molecular orbital calculations, (four-electron, three-centre model with neglect of the P d orbitals)18,19 semiempirical calculations20,21 non-empirical calculations22,23 and hybrid orbitals24,25. 

The Disease-Centred Model of Drug Action in Psychiatry ... 

Table 1.1 Alternative models of drug action Disease-centred model Drug-centred model...

The pharmaceutical industry employs similar language in its promotional material. An early advertisement for Prozac suggests that Like arthritis or diabetes, depression is a physical illness (Valenstein 1988, reproduced on p. 181). A leaflet produced in 1996 by a consortium called America s Pharmaceutical Research Companies neatly summarises the idea of the chemical imbalance and its relation to a disease-centred model of drug action ... 

This book concerns the creation of a myth, the myth of the disease-centred model of drug action, and how that myth could be accepted as a real description of the world. It therefore involves questions about the nature of knowledge and the relation between knowledge and power. 

My thesis in this book is that the disease-centred model of drug action has been adopted, and recently widely publicised, not because the evidence for it is compelling, but because it helped promote the interests of certain powerful social groups, namely the psychiatric profession, the pharmaceutical industry and the modern state. Therefore, I offer the following study as an example of the way in which vested interests and the political environment can distort knowledge, in this case successfully deluding most of society for over half a century. 

The case of alcohol illustrates how a drug-centred model can clarify the potential therapeutic uses of drugs for psychiatric or behavioural problems. Alcohol is a sedative drug that reduces nerve conductivity in the central nervous system. Ingestion of alcohol gives rise to characteristic physiological effects, such as dilation of blood vessels, smooth... 

Since standard clinical trials cannot distinguish between a drug s action on a disease process and the consequences of the abnormal state a drug induces, other sorts of evidence set out below are necessary to discriminate between the disease-centred and the drug-centred model. In the following chapters I will examine these types of evidence for different classes of drugs ... 

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