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SB-699,551 structure.png
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Molar mass511.739 g/mol g·mol−1
3D model (JSmol)

SB-699551 is a drug which was the first compound developed to act as a selective antagonist for the serotonin receptor 5-HT5A, with selectivity of around 100x over other serotonin receptor subtypes.[1] The function of the 5-HT5A receptor remains poorly defined, but SB-699551 was found to modulate serotonin release from neurons, suggesting it acts as a presynaptic inhibitory autoreceptor similar to the 5-HT1B and 5-HT1D receptors.[2] Multiple therapeutic roles have been suggested for 5-HT5A ligands due to the presence of this receptor in several areas of the brain, but research is still at an early stage,[3] with one possible application being the currently difficult to treat negative symptoms of schizophrenia.[4] In animal studies, SB-699551 was found to block cue-mediated responding to LSD, again suggesting an antipsychotic type of activity.[5]


  1. ^ Corbett, DF; Heightman, TD; Moss, SF; Bromidge, SM; Coggon, SA; Longley, MJ; Roa, AM; Williams, JA; Thomas, DR (2005). "Discovery of a potent and selective 5-ht5A receptor antagonist by high-throughput chemistry". Bioorganic & Medicinal Chemistry Letters. 15 (18): 4014–8. doi:10.1016/j.bmcl.2005.06.024. PMID 16002289.
  2. ^ Thomas DR, Soffin EM, Roberts C, Kew JN, de la Flor RM, Dawson LA, Fry VA, Coggon SA, Faedo S, Hayes PD, Corbett DF, Davies CH, Hagan JJ. SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain. Neuropharmacology. 2006 Sep;51(3):566-77. PMID 16846620
  3. ^ Thomas, DR (2006). "5-ht5A receptors as a therapeutic target". Pharmacology & Therapeutics. 111 (3): 707–14. doi:10.1016/j.pharmthera.2005.12.006. PMID 16516972.
  4. ^ Nikiforuk A, Hołuj M, Kos T, Popik P. The effects of a 5-HT5A receptor antagonist in a ketamine-based rat model of cognitive dysfunction and the negative symptoms of schizophrenia. Neuropharmacology. 2016 Jun;105:351-60. doi:10.1016/j.neuropharm.2016.01.035. PMID 26826431
  5. ^ Popik P, Krawczyk M, Kuziak A, Bugno R, Hogendorf A, Staroń J, Nikiforuk A. Serotonin type 5A receptor antagonists inhibit D-lysergic acid diethylamide discriminatory cue in rats. J Psychopharmacol. 2019 Aug 27:269881119867603. PMID 31452444 doi:10.1177/0269881119867603