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Access through your institution Buy or subscribe The authors looked at the α2A-adrenoceptor (α2A-AR), as genetic manipulation of this receptor in mice had shown that it was involved in
several responses — both clinically desired (for example, hypotension) and unwanted (for example, sedation). So, they were surprised to find that in heterozygous models (_α__2A__-AR_+/−
mice) supramaximal doses of α2A-agonists lowered blood pressure without affecting sedation, implying that more than 50% of α2A-AR must be activated to cause sedation. Limbird and colleagues
hypothesized that differing fractional activation of receptors by using partial agonists (or alternatively by administering incremental doses of a full agonist) could produce these selective
responses. This idea was supported by the fact that moxonidine (which the authors showed to be a partial agonist in _in vitro_ studies) has no hypotensive effects in α2A-AR-null mice but
lowers blood pressure without sedation in wild-type mice. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to
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support REFERENCES ORIGINAL RESEARCH PAPER * Tan, C. M., Wilson, M. H. MacMillan, L. B., Kobilka, B. K. & Limbird, L. E. Heterozygous α2A-adrenergic receptor null mice unveil unique
therapeutic benefits of partial agonists. _Proc. Natl Acad. Sci. USA_ 99, 12471–12476 (2002) Article CAS PubMed Google Scholar FURTHER READING * Kenakin, T. Efficacy at G-protein-coupled
receptors. _Nature Rev. Drug Discov._ 1, 103–110 (2002) Article CAS Google Scholar Download references Authors * Simon Frantz View author publications You can also search for this author
inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Frantz, S. Sorting good from bad. _Nat Rev Drug Discov_ 1, 750 (2002).
https://doi.org/10.1038/nrd932 Download citation * Issue Date: 01 October 2002 * DOI: https://doi.org/10.1038/nrd932 SHARE THIS ARTICLE Anyone you share the following link with will be able
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