Inactivation of monoamines by the lung

Inactivation of monoamines was the first pharmacokinetic property of lung to be identified. For some amines inactivation in perfused lung but not in liver is limited by uptake. Inactivation of beta-phenylethylamine in lung is limited not by uptake but by the activity of intracellular monoamine oxidase. The uptake of this amine is like that of basic drugs such as amphetamine and propranolol. Changes in the external environment of the lung (exposure in vivo to gaseous anaesthetics or to high concentrations of oxygen, greater than 95%) change amine inactivation processes in lung. The oestrous cycle and administration of ovarian steroids also affect the inactivation of 5-hydroxytryptamine and phenylethylamine. Monoamine oxidase activity in lung homogenates is highest at met- and lowest at pro-oestrus for both substrates. However, in perfused lung, inactivation is better correlated with variations in uptake. Therefore the main effect of the oestrous cycle is on uptake rather than on enzymic activity. Uptake processes are thus crucial determinants of monoamine activation in lung and the pharmacokinetic properties of lung are capable of responding to changes in its internal or external environment.