Serotonin 5-HT1A receptor

Every compound in the sci-wiki that affects serotonin 5-ht1a receptor; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

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Anxiolytic

Adatanserin

Adatanserin is an azapirone-like compound developed by Wyeth (as WY-50324) as a combined anxiolytic and antidepressant. Structurally it is an adamantane bolted onto a pyrimidinylpiperazine, the same piperazine motif found in buspirone. Pharmacologically it does two things at once: it partially activates the serotonin 5-HT1A receptor and blocks the 5-HT2 (chiefly 5-HT2A) receptor, a dual profile thought to combine calming and mood-lifting actions. It reached early development but was not marketed; the published work is preclinical, from the 1990s and a few later chemistry papers.

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Serotonergic

WAY-100635

WAY-100635 is the molecule that a very large part of what is known about the serotonin 5-HT1A receptor was measured with. Wyeth described it across 1995 and 1996 as the first potent, selective and silent antagonist at that receptor: it displaced tritiated 8-OH-DPAT from rat hippocampal 5-HT1A sites with an IC50 near 1.35 nM, blocked every classical 5-HT1A agonist response tested, and produced none of those responses itself [2][3]. That combination is rarer than it sounds, and it made the compound a fixture; well over a thousand published papers now use it, nearly always in the same design, where an effect is produced with a serotonin agonist and then removed with WAY-100635 to show which receptor carried it. Labelled with carbon-11 on the cyclohexanecarbonyl group it also became the standard positron emission tomography tracer for mapping 5-HT1A receptors in living human brain [17][29]. The reputation for cleanliness was later challenged. A 2006 screen reported low nanomolar binding and full agonist activity at dopamine D4 receptors and said outright that conclusions resting on WAY-100635 as a selective 5-HT1A antagonist may need re-examining [9]; a second laboratory measured the same receptor and reached almost the opposite conclusion [10]. That argument is not settled. WAY-100635 has never been given to anyone as a medicine, and the only human exposure on record is a microgram tracer dose in a brain scan.

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