The concept of selectivity in 5-HT receptor research.
Since the demonstration that serotonin (5-hydroxytryptamine, 5-HT) interacts with different (sub)types of membrane receptors, several compounds have been proposed as potent and selective ligands for one of these 5-HT subtypes. Unfortunately, specific and highly selective ligands (selectivity ratios greater than or equal to 1000) for the majority of 5-HT subtypes are still lacking. A few compounds are selective (ratios greater than or equal to 100), but most of the reputed 'selective' tools display affinities for other 5-HT subtypes and/or other (neuro-) transmitter receptors. Mainly due to different interpretations of the concept of selectivity, many of these nonselective compounds are still used to characterize 5-HT receptors. In this paper, we present the affinities (obtained by radioligand binding studies) of the most selective tools known today for each of the 5-HT subtypes and discuss the structure-activity relationships of some interesting series. The potential use of several of these selective ligands as pharmacological tools and therapeutics will be briefly reviewed.
van Wijngaarden
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Department of Medicinal Chemistry, Duphar B.V., Weesp, The Netherlands.
Tulp
M T
MT
Soudijn
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D000818:Animals; D006801:Humans; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin