Ionised drugs activity

The coexistence of lipid and water solubility in the same molecule is essential for the action of a local anaesthetic drug. Lipophilicity permits the migration of drug across the phospholipid membrane of the nerve cell hydrophilicity is essential for the ionisation of the drug within the nerve. It follows that lipid and water solubility are the external and internal facilitators of local anaesthetic action in the nerve cell. Both within and without the nerve cell the unionised and ionised forms coexist in dynamic equilibrium. Outside the nerve, the active species is the unionised tertiary amine form. Conversely, inside the cell the ionised form predominates. The lower intracellular pH induces a shift in the equilibrium in favour of ionisation (Figure 5.5). 

The sodium salts of the barbiturates (monoanions) are usually quite soluble in water, and this is normally the preferred form of the drugs for therapeutic use. The stability and hydrolysis products of barbiturate salts have been reviewed in detail elsewhere [99], and will not be discussed here. The anions of the barbiturates are not soluble in lipids, and the non-ionised form of the hypnotic barbiturates is considered to be the active form of the drugs. Hence, an accurate knowledge of their dissociation constants and the pH values of solutions under the conditions of a given experiment are of considerable importance. The relationship of physical properties to physiological activity is discussed in the following section on the hypnotic barbiturates. 

Atkinson SJ, Loadman PM, Sutton C, Patterson, LH, Clench MR. Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom 2007 21 1271-1276. 

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