Current problems and future requirements for 5-hydroxytryptamine receptor classification.

The present scheme for classifying and naming 5-hydroxytryptamine (5-HT) receptors is being challenged by a growing number of reports that describe receptor types that fail to meet the criteria for admission into the "5-HT1-like," 5-HT2 or, 5-HT3 classes. Consequently, there is an increasing tendency for authors to make unilateral designations for new receptor classes in the absence of any formal criteria for their classification. This hinders rather than helps in establishing the minimum safe criteria for receptor definition and emphasizes the need to update the current scheme. In this article a number of factors are considered that might contribute to instability in 5-HT receptor classification and attention is drawn in particular to the generally unreliable behavior of available chemically heterogeneous antagonists. Experiments with tryptamine agonists and antagonists, although limited in number, suggest that close chemical analogs of the natural receptor agonist 5-HT provide a quantitatively stable and therefore more secure basis for classification, which usefully complements and extends the currently accepted proposals. Furthermore, an approach based on hormone analogs focuses attention on the objectives of the classification process as well as a definition for the term receptor. These issues are germane to the development of a unifying scheme for receptor taxonomy and have been considered here in terms of the current problems and future requirements of 5-HT receptor classification.