Spanners in the works
What do pharmaceuticals actually do?
Drugs interfere with our biochemistry. Usually, they stop something happening (inhibitors); sometimes they kick a biochemical process into life (activators).
The molecule that a drug acts on is its target. Targets need to be accessible, so they are commonly molecules on the surface of cells, such as receptors for signalling molecules. Binding of the drug prevents it being activated by its ligand.
Drugs may also bind to ion channels (pores in the cell membrane that trafﬁc ions into or out of the cell) or target molecules that transmit signals between cells.
Ever since Paul Ehrlich proposed the idea of a ‘magic bullet’, drug development has sought ‘clean’ compounds. A clean drug is highly specific – it will bind only a single type of receptor or channel, meaning fewer unexpected side-effects occur. Drugs that bind multiple different receptors or channels are described as ‘dirty’ and have traditionally been considered undesirable therapeutically, but there are indications that ‘dirty’ compounds might also be useful.
Part of the rationale comes from studies of antipsychotic drugs (e.g. clozapine for schizophrenia, which binds to at least 17 different receptors). Now it is known which receptors they recognise, they have been reﬁned chemically to try to reduce cross-reaction and side-effects. Unfortunately, cleaner versions don’t work – dirtiness seems to be crucial to their effects.
Some researchers are now talking in terms of a ‘magic shotgun’, with agents taking out several targets simultaneously. For complex diseases, where multiple interacting biochemical pathways may be inﬂuencing a disease process, a shotgun might be a better weapon than a riﬂe.