Use of knockout technology to resolve pharmacological problems.

Knock-out (KO) mouse technology has given pharmacologists a powerful tool to study function in the absence of selective antagonists or inhibitors. Such KO technology can confirm predicted function, serendipitously reveal unrecognized function, or help define the mode of action of a drug. In this issue, Liles et al. demonstrate, employing mice unable to synthesize noradrenaline due to the KO of the dopamine-beta-hydroxylase gene, that the sympathomimetic actions of ephedrine are directly, rather than indirectly, mediated. This may end 50 years of debate about the actions of ephedrine.