Hapten hypothesis

An alternative theory to the hapten hypothesis that goes some way to explain why not all drugs that form reactive intermediates are associated with idiosyncratic reactions... 

In order to explain the stimulation of an immune response by small drug molecules, Landsteiner in the 1930 s showed that small molecules could stimulate an immune reaction if combined with a protein. This became the hapten hypothesis, that small molecules could be... 

Furthermore, there are many unanswered questions regarding idiosyncratic drug toxicity mediated by immune mechanisms, and the above explanations are not always sufficient. Some cases do not fit into the classical hapten hypothesis model. For example, antidrug antibodies are not always detectable. Immune reactions can take a period of months or even years to develop (e.g., hydralazine see below). 

The hapten-hypothesis proposes that sensitizing low molecular weight (i.e. too small to be recognized by T cells directly) drugs conjugate to proteins that... 

Probably the most unique feature of 1 is the presence of the methylene spacer between the 2-position of the carbapenem nucleus and the nitrogen of the naphthosultam. Because of concerns that the residues of these carbapenems might illicit an immune response once they acylated a blood borne protein, the methylene spacer was put between the two components of the molecule to allow it to fragment after acylation. Thus, the side chain would become available for normal metabolic-elimination processes, and the bound residue of the carbapenem would be too small to effect the immune reaction. Internally, this became knows as the releasable hapten hypothesis , and served to generate a number of exciting new compounds. (Figure 1). ... 

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