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Scheinin, Professor of Clinical Pharmacology, Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland. Chemical names HF2035: 2-[2-aminoethyl]-N-[2,4,5-trichlorobenzene- sulphonyl] amino-N-[4-chlorocinnamyl]N-methylben- zylamine LY83583: 6-anilino-5,8-quinolinedione HF2035: 2-[2-aminoethyl]-N-[2,4,5-trichlorobenzene- sulphonyl]amino-N-[4-chlorocinnamyl]N-methyl- benzylamine Gene targeting – homing in on  2 -adrenoceptor- subtype function Ewen MacDonald, Brian K. Kobilka and Mika Scheinin The  2 -adrenoceptor was subdivided into three subtypes:  2A -,  2B - and  2C -adrenoceptors almost ten years ago. Since then, the search has been on to discover and develop subtype-selective agonists and antagonists, but as yet no major breakthrough has been made. In the past year, several strains of genetically engineered mice have become available, either overexpressing, totally lacking or expressing heavily modified  2 -adrenoceptor subtypes. Ewen MacDonald, Brian Kobilka and Mika Scheinin describe how these mice may be utilized to elucidate the physiological functions of the receptor subtypes and the properties of future subtype-selective drugs. One of the greatest contributions that molecular biology has made to pharmacology is the clarification of receptor classification, particularly the functional contributions of varying receptor subtypes. Before molecular cloning as a means for receptor identification, classification of a new receptor subtype relied on pharmacological methods (e.g. order of agonist potency) that were often confounded in interpretation due to variable receptor reserve in different tissues or the exploitation of differing effectors in different settings by receptor subpopulations. Currently, receptor subtypes are often cloned before specific ligands binding to them are available, i.e. so-called orphan receptors posing a new set of challenges for pharmacologists and the pharmaceutical industry. In many ways, the  2 -adrenoceptors exemplify the above scenario. There are now three well characterized receptor subtypes;  2A ,  2B and  2C (Ref. 1; Table 1). However, available ligands have only marginal subtype selectivity. This review will describe strategies other than the evaluation of subtype-selective ligands to allo- cate physiological effects to distinct  2 -adrenoceptor subtypes and subsequently predict the pharmacological and therapeutic properties of subtype-selective drugs under development.