Isomerism is the phenomenon by which molecules with the same atomic formulae have different structural arrangements – the component atoms of the molecule are the same, but they are arranged in a different configuration. There are two broad classes of isomerism:

• Structural isomerism

• Stereoisomerism

Structural isomerism

Molecules that are structural isomers have identical chemical formulae, but the order of atomic bonds differs. Depending on the degree of structural similarity between the isomers, comparative pharmacological effects may range from identical to markedly different. Isoflurane and enflurane are both volatile anaesthetic agents; prednisolone and aldosterone have significantly different activities, with the former having glucocorticoid and mineralocorticoid actions but the latter being predominantly a mineralocorticoid. Isoprenaline and methoxamine have different cardiovascular effects, with methoxamine acting predominantly via α-adrenoceptors and isoprenaline acting via β-adrenoceptors. Dihydrocodeine and dobutamine are structural isomers with very different pharmacological effects; it is little more than coincidence that their chemical formulae are identical (Figure 5.1).

Tautomerism

Tautomerism refers to the dynamic interchange between two forms of a molecular structure, often precipitated by a change in the physical environment. For example, midazolam, which is ionized in solution at pH 4, changes structure by forming a seven-membered unionized ring at physiological pH 7.4, rendering it lipid-soluble, which favours passage through the blood–brain barrier and increases speed of access to its active sites in the central nervous system (see Figure 17.1). Another common form of isomerism is the keto-enol transformation seen in both morphine and thiopental.