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The a,-adrenoceptor agonists may become an attractive alternative to the currently used analgesics because they are devoid of respiratory depressant effect and addictive liability. However, some of their pharmacologic properties, namely sedation and hypotension, are hindering the clinical use of subtype nonselective a,-adrenoceptor agonists for pain management in the ambulatory setting. This has provoked two parallel lines of investigation to elucidate which function each of the three subtypes (i.e., aZA, aLR, and arc) mediates and to define the distribution of the subtypes. The study by Ongjoco et al. ’ in this issue of ANESTHESKXOGY sheds further light on this issue. The ratiotiale for this approach is to identify a single receptor subtype target that mediates the desired analgesic effect and is incapable of producing the undesirable pharmacologic properties. Armed with this information, chemists can then direct a “target-based’’ dnig-design program to synthesize a novel, subtype-selective, a,-adrenoceptor agonist. The genes for each of these receptor subtypes have been cloned, making it possible to investigate their transcription, expression, and their role in physiologic and pathologic settings. The mRNA transcription patterns of these receptor subtypes can be elucidated qualitatively (e.g., by in situ hybridization) and quantitatively (c~g., by northern assay, ribonuclease protection assay or reverse-transcription polymerase chain reaction [RTPCR] assay). Furthermore, recombinant DNA methodology has made it possible to address the role of the

α2Adrenoceptors in Pain Modulation : Which Subtype Should Be Targeted to Produce Analgesia?