5-HT receptor pharmacology and location in the CV system
Values in parenthese are Ki values. Cloned indicates that values are only from cloned, transfected receptors. Affinity values are from averaged experiments available on http://pdsp.med.unc.edu/indexR.html. Modified from Watts, 2005.
| Receptor | Agonists | Antagonists | Location and Response Relevant to Blood Pressure | |
|---|---|---|---|---|
| Heptahelical |  | |||
| Ion channel |  | |||
| 5-HT1A (2.65 nM) |  | 8-OH-DPAT, U92016A | WAY100635, NAN190 | Central nervous system (lower, raise blood pressure) |
| 5-HT1B (16.01 nM) |  | CP-93129, sumatriptan, eletriptan (some 1D affinity) | GR-127935 (some 1D affinity), GR55562, isamoltane, SB236057 | Smooth muscle (contraction); sympathetic presynaptic terminal (inhibition of NE release); sympathetic ganglia (inhibit transmission); central nervous system (lower, raise blood pressure) |
| 5-HT1D (10.05 nM) |  | PNU-109291, alniditan, eletriptan (some 1B affinity), L-703,664 | SB 272183, LY310762, BRL15572 | Smooth muscle (contraction) |
| 5-ht1Ea (7.00 nM, cloned) |  | 5-CT (nonselective), BRL54443 (some 1F affinity) | None available | None identified |
| 5-HT1F (67.60 nM, cloned) |  | LY334370, BRL54443 (1E affinity), LY344864 | None available | Smooth muscle (contraction), trigeminal nerve |
| 5-HT2A (970.80 nM) |  | DOB (2A/2B, 2C), DOI, α-methyl-5-HT (non-selective), TCB-2 | R-96544, MDL100907, volinanserin | Platelet (aggregation and 5-HT release); smooth muscle (contraction); adrenal gland (epinephrine release); heart (tachycardia, contraction); central nervous system |
| 5-HT2B (11.35 nM) |  | BW723C86 | LY272015, RS127445 | Endothelium (relaxation); smooth muscle (contraction); cardiac valves (proliferation) |
| 5-HT2C (32.58 nM) |  | WAY 163909, DOI (2A, 2B, 2C), MK212, 1-methylpsilocin | RS102221, SB242084 | None identified |
| 5-HT3 (splice variants) (190.33 nM) |  | SR57227A, 2-methyl-5-HT, phenylbiguanide | Odansetron, granisetron | Vagus nerve (bradycardia); ganglia |
| 5-HT4(short,long) (117.00 nM, cloned) |  | RS67506, BIMU1, BIMU8, zacopride | GR113808, RS100235, SB204070 | Cardiomyocyte (contraction) |
| 5-HT6 (116.53 nM, cloned) |  | WAY 181,187, EMD 386088 | Ro 04-6790, SB 399885, SB271046 | None identified |
| 5-HT7(a–d) (3.65 nM, cloned) |  | LP12, LP44, AS-19, 5-CT (nonselective) | SB-269970, SB-258719 | Smooth muscle (relaxation); cardiomyocyte (contraction) |
↵* No physiological response has been associated with receptor, hence lower case.
AS-19, (2S)-(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2-(dimethylamino)tetralin; BIMU1, endo-N-(8-methyl-8-azabicyclo-[3.2.1] oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazole-1-carboxamide; BIMU8, 2,3-dihydro-N-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-3-(1-methylethyl)-2-oxo-1H-benzimidazole-1-carboxamide; BRL15572, 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; BRL54443, 5-hydroxy-3-(1-methylpiperidin-4-yl)-1H-indole; BW723C86, α-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine; CP-93129, 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl-5H-pyrrol[3,2-b]pyridin-5-one; DOI, 2,5-dimethoxy-4-iodoamphetamine; EMD 386088, 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole; GR113808, 1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester; GR-127935, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1′-biphenyl-4-carboxamide; GR55562, 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide; L-703,664, N,N-dimethyl-5-[(5-methyl-1,1-dioxodo-1,2,5-thiadiazolidin-2-yl)methyl]-1H-indole-3-ethanamine; LP12, 4-(2-diphenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide; LP44, 4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide; LY272015, 1-[(3,4-dimethoxyphenyl)methy]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-b]indole; LY310762, 1-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-1,3-dihydro-3,3-dimethyl-2H-indol-2-one; LY334370, 4-fluoro-N-(1-methyl-4-piperidinyl)-1H-indol-5-yl]-benzamide; LY344864, N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]-4-fluorobenzamide; MDL100907, (2,3-dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol; MK212, 6-chloro-2-(1-piperazinyl)pyrazine; NAN190, 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine; PNU-109291, (S)-3,4-dihydro-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-1H-2-benzopyran-6-carboxamide; R-96544, (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrolidinol; Ro 04-6790, 4-amino-N-[2,6-bis(methylamino)-4-pyrimidinyl]-benzenesulfonamide; RS100235, 1-(5-amino-6-chloro-2,3-dihydro-1,4-benzodioxin-8-yl)-3-[1-[3-(3,4-dimethoxyphenyl)propyl]piperidin-4-yl]propan-1-one; RS102221, 8-[5-(2, 4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione; RS127445, 4-(4-fluoro-1-naphthalenyl)-6-(1-methylethyl)-2-pyrimidinamine; RS67506, 1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1–2-methylsulphonylamino)ethyl-4-piperidinyl]-1-propanone; SB204070, (1-butyl-4-piperidinyl)methyl-8-amino-7-chloro-1,4-benzodioxane-5-carboxylate; SB236057, 1′-ethyl-7-({4-[2-methyl-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]phenyl}carbonyl)-2,5,6,7-tetrahydrospiro[furo [2,3-f]indole-1,4′-piperidine]; SB242084, 6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride; SB258719, 3-methyl-N-[(1R)-1-methyl-3-(4-methyl-1-piperidinyl)propyl]-N-methylbenzenesulfonamide; SB269970, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine; SB271046, 5-chloro-N-[4-methoxy-3-(1-piperazinyl)phenyl]-3-methyl-benzo[b]thiophen-2-sulfonamide; SB272183, 5-chloro-2,3-dihydro-6-(4-methylpiperazin-1-yl)-1(4-pyridin-4-yl)napth-1-ylaminocarbonyl]-1H-indole); SB399885, N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-(1-piperazinyl)benzenesulfonamide; SB699551, N-[2-(dimethylamino)ethyl]-N-[[4′-[[(2-phenylethyl)amino]methyl][1,1′-biphenyl]-4-yl]methyl]cyclopentanepropanamide; SR57227A, 1-(6-chloro-2-pyridinyl)-4-piperidinamine; U92016A, (R)-8-dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indole-2-carbonitrile; WAY 100635, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide; WAY 163909, [(7bR, 10aR)-1,2,3,4,8,9,10, 10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1-hi]indole]; WAY 181,187, 2-(1-{6-chloroimidazo[2,1-b][1,3]thiazole-5-sulfonyl}-1H-indol-3-yl)ethan-1-amine.