5-HT Receptor

Brilaroxazine (RP5063): multimodal dopamine/5-HT modulator, partial agonist at D2/D3/D4, 5-HT1A/2A, and antagonist at 5-HT2B/7.

Bexicaserin (Compound 3), a 5-HT2C receptor agonist, has potential applications in research pertaining to obesity and psychiatric disorders [1].

13,14-dihydro-15-keto Prostaglandin E2 (13,14-dihydro-15-keto PGE2) serves as the predominant metabolite of PGE2 in plasma, created through a 15-keto PGE2 intermediate by the action of 15-oxo-PG Δ13 reductase. Unlike its precursor PGE2, this compound exhibits poor binding affinity towards EP2 and EP4 PGE2 receptors (Ki values of 12 and 57 µM, respectively) in CHO cells and fails to stimulate adenylate cyclase activity therein (EC50s >18 and >38 µM, respectively). Concentrations of 13,14-dihydro-15-keto PGE2 are notably higher in the plasma of pregnant women during their third trimester and at labor and delivery stages, whereas its levels are found to be reduced in the tumor tissues of patients with non-small cell lung cancer (NSCLC) compared to adjacent healthy tissue.

Amesergide is an orally active and selective serotonin (5-HT1/2) antagonist that inhibits weight gain in offspring of female CD rats, for depression research.

PNU109291, a potent and selective agonist of the 5-HT1D receptor, effectively mitigates dural plasma extravasation induced by trigeminal ganglion stimulation.

SB 258719 is a selective antagonist of 5-HT7 receptor with pKi of 7.5.

5-HT2A receptor agonist-3 represents the highest selectivity for the human 5-HT2A receptor currently identified, exhibiting a K i of 2.5 nM.

R-96544 is an orally active antagonist of the 5-HT2A receptor that has demonstrated the ability to inhibit platelet aggregation in vitro [1].

5-HT3 antagonist 1 is a potent and selective antagonist of 5-HT3 receptor.

L-772,405 is a highly selective agonists of h5-HT(1D) receptor.

SB 649915 is a serotonin reuptake inhibitor and 5-HT1A and 5-HT1B receptor antagonist.

Velusetrag(TD-5108), a potent 5-HT4 agonist, is in development for gastroparesis, constipation, and IBS.

FK1052 hydrochloride is a potent 5-HT3 and 5-HT4 receptor dual antagonist.

Selective, high affinity 5-HT1A receptor antagonist

GR 125487 sulfamate is a 5-HT4 receptor antagonist.

Flesinoxan HCl is the salt form of Flesinoxan, which is a selective 5-HT1A receptor agonist.

NAS-181 free base is a 5-HT(1B) receptor antagonist.

(S)-Renzapride (BRL 24924), 5-HT4 agonist (Ki 115 nM), 5HT2b/5HT3 antagonist, for C-IBS study.

UNC9994 is a β-arrestin-biased dopamine D₂ receptor agonist (β-arrestin EC50 = 50 nM; Emax = 97%) with robust in vivo antipsychotic drug-like activities.

Facinicline hydrochloride (RG3487) is both a novel nicotinic alpha-7 receptor (alpha7nAChR) partial agonist (Ki = 6 nM) and an antagonist of 5-HT3(Ki = 1.2 nM).

2-Methyl-5-HT (2-Methyl-5-hydroxytryptamine) is a potent and selective 5-HT3 receptor agonist with anti-depressive-like effects.

5-HT1B/1D receptor antagonist

1-Carboxycyclohexaneacetic acid may be present as a potential impurity in commercial gabapentin, an antiepileptic drug. Furthermore, it serves as a precursor for synthesizing antagonists targeting the serotonin (5-HT) receptor subtype 5-HT2A.

Wf-516 is a 5-HT reuptake inhibitor (Kis: 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively), and with potent antidepressant

MDL-74156 is an active metabolite of dolasetron and a 5-hydroxy-tryptamine3 (5-HT3) antagonist.

Butriptyline (Butriptylene), a tricyclic antidepressant, is effective when administered orally [1].

Abaperidone is an atypical antipsychotic, antagonizes 5-HT2A (IC50=6.2 nM) and D2 receptors (IC50=17 nM), reduces hsp70 mRNA in rat brains.

Indeloxazine HCl: Serotonin releaser, NE reuptake inhibitor, NMDA antagonist; antidepressant that boosts acetylcholine in rats.

FK-1052 is a serotonin 3 & 4 dual receptor antagonist.

5-HT2C agonist-3 ((+)-19), a selective 5-HT2C agonist (EC 50: 24 nM, Ki: 78 nM), exhibits antipsychotic-like activity by blocking amphetamine-induced

Compound 24 (5-HT2 agonist-1 free base) is a potent agonist for 5-HT2A, 5-HT2B, and 5-HT2C receptors, exhibiting IC50 values of 10 nM, 8.3 nM, and 1.6 nM,

4-Chloro-L-phenalanine (L-PCPA) is an inhibitor of 5-HT biosynthesis and a non-specific antagonist of tryptophan hydroxylases (TPH1 and TPH2).

LY320954 is an antagonist of 5-HT2A receptor.

YM348 is an effective and orally active 5-HT2C receptor agonist. YM348 also shows a high affinity for the cloned human 5-HT2C receptor (Ki: 0.89 nM).

GR-127935 is a potent and selective 5-HT1B/1D receptor antagonist.

Frovatriptan, potent 5-HT 1B/D agonist, shows high cerebroselectivity and efficacy for migraine with aura.

Robalzotan is a selective 5-HT1A receptor antagonist.

rat 5-HT1B receptor antagonist

Osemozotan Free Base is a 5-HT(1A) receptor agonist.

Compound 24, a 5-HT2 agonist-1, selectively activates 5-HT2A, 5-HT2B, and 5-HT2C receptors with IC50 values of 10 nM, 8.3 nM, and 1.6 nM, respectively.

CP-122288: potent, selective 5-HT1B/D/F agonist; inhibits plasma protein extravasation, neurogenic inflammation.

MIN-117, a SSRI/5-HT receptor antagonist, is potentially used for the treatment of depression.

5-HT2A&5-HT2C agonist-1 (Example 2) is a dual-acting agent targeting the 5-HT2A and 5-HT2C receptors with respective IC50 values of 196 nM and 0.9 nM.

Nemonapride is a dopamine D2-like receptor antagonist.

5-HT3-In-1 (compound example 8) exhabits with 5-HT3 inhibition activity.

(S)-Bexcaserin (compound 2) serves as a 5-HT2C receptor agonist, presenting research possibilities in obesity and psychiatric disorders [1].

SB 216641 hydrochloride (SB-216641A) is a 5-HT1B/D receptor antagonist with anxiolytic properties.

WAY-607695 is a potential 5-HT1A receptor agonist.

Didesmethyl cariprazine, Cariprazine's active metabolite, treats schizophrenia/bipolar with D3/D2 affinity; half-life 1-3 weeks.

Osemozotan is a 5-HT1A receptor agonist potentially for the treatment of generalized anxiety disorder.

SB-616234-A is a selective and orally bioavailable antagonist of 5-HT1B receptor, with anxiolytic and antidepressant activity.

Lumateperone (ITI 722) is a 5HT2A receptor antagonist and a dopamine receptor phosphoprotein modulator (DPPM).

Tiprenolol hydrochloride is a β-adrenoceptor (β-adrenoceptor) antagonist. This compound is effective in eliminating ventricular arrhythmias in dogs caused by intravenous administration of adrenaline, following inhalation of halothane.

AM9405: peripheral CB1/5-HT3 agonist, suppresses gut motility, relieves GI disorder symptoms in mice.

SB 224289: selective 5-HT1B antagonist, pKi 8.2, 60x selectivity, effective orally.

F 14679 is a potent 5-HT1A agonist (pKi=10.23) with a maximum Ca2t response similar to 5-HT.

5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.

SB 243213 hydrochloride is an orally active, selective and high-affinity antagonist of 5-hydroxytryptamine (5-HT)2C receptor(pKi of 9.37 and a pKb of 9.8).It

Beloxepin is an oral dual selective inhibitor of serotonin and norepinephrine uptake.

Compound (−)-19, also known as (-)-5-HT2C agonist-3, is a selective 5-HT2C agonist exhibiting a preference for Gq signaling. It demonstrates efficiency with EC50 values for 5-HT2 receptor subtypes as follows: 5-HT2C at 103 nM, 5-HT2B at 570 nM, and 5-HT2A at 72 nM. This compound is utilized in research on antipsychotics.

AAZ-A 154 hydrochloride is a selective, competitive, non-hallucinogenic antagonist of 5-HT2AR. It promotes neuronal growth in rodents and results in enduring beneficial behavioral effects.

5-HT1A modulator 4 (Compound 1) is a ligand for the 5-HT receptor, with Ki values of 2.18 μM for 5-HT1A and 19.7 μM for 5-HT2A.

THRX-194556 is an agonist of the 5-HT4 receptor. It is applicable in the study of gastrointestinal functional disorders and Alzheimer's disease.

Compound 6.4, also known as 5-HT7R antagonist 3, is a selective antagonist of the 5-HT7R with a Ki of 8 nM. It exhibits significantly less affinity towards D2R, 5-HT1AR, and 5-HT2AR with Ki values of 511 nM, 8930 nM, and 5786 nM, respectively. In mice, 5-HT7R antagonist 3 demonstrates anti-depressant and anti-anxiety activities.

AChE-IN-5: oral, crosses blood-brain barrier, targets AChE/5-HT1A/SERT, potent with 2.29 nM IC50.

Compound 6f is a potent, selective 5-HT1A receptor blocker (Ki: 35 nM), useful in CNS disorder research.

5-HT2A and 2C receptor antagonist

Potent 5-HT6/5-HT2A receptors dual antagonist with K i of 11 nM & 39 nM.

Rodatristat is an effective tryptophan hydroxylase 1 and TPH2 inhibitor (IC50s: 33 nM and 7 nM, respectively).

D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.

25B-NBOH hydrochloride is a phenethylamine that exhibits high affinity for serotonin (5-HT) receptors 5-HT2A and 5-HT2C, with pKi values of 8.3 and 9.4, respectively.

SB 243213 dihydrochloride is an orally active, selective and high-affinity antagonist of 5-hydroxytryptamine (5-HT)2C receptor(pKi of 9.37 and a pKb of 9.8 for

5-IAI hydrochloride is a psychoactive analog of para-iodoamphetamine. 5-IAI hydrochloride significantly reduces serotonin uptake sites and hippocampal serotonin levels in rats.

Ro4368554 is a selective 5-HT6 antagonist capable of crossing the blood-brain barrier. It can reverse memory deficits caused by scopolamine and tryptophan depletion. Ro4368554 is applicable for research related to memory impairments.

LB-102 is an orally active inhibitor of dopamine D2, D3, and serotonin 5-HT7 receptors, utilized in the study of schizophrenia and other psychiatric disorders.

Revexepride, a 5-HT4 agonist, may boost CYP3A4, used for treating GERD.

LP 12 hydrochloride hydrate: potent, selective 5-HT7 agonist (Ki: 0.13 nM); less affinity for D2, 5-HT1A/2A receptors.

Befiradol HCl (NLX-112) is a selective 5-HT1A receptor agonist with anxiolytic effects and prevents ATXN3 aggregation.

(S)-Praziquantel is the inactive isomer of R-praziquantel.

Compound 2o, also known as CB2R/5-HT1AR agonist 1, serves as a partial orally active agonist for the CB2 receptor (EC50 = 479.6 nM) and a full agonist for the 5-HT1A receptor (EC50 = 2.7 μM). This compound demonstrates both anti-anxiety and anti-depressive effects and has favorable pharmacokinetic properties [1].

VA012 (compound 11) acts as a positive allosteric modulator (PAM) of the serotonin 5-HT2C receptor. It has been shown to reduce food intake and prevent weight gain during subchronic administration without causing central nervous system-related discomfort. VA012 is applicable in obesity research.

5-HT2A/5-HT2C inverse agonist 1 serves as a dual and potent inverse agonist for the 5-HT2A and 5-HT2C receptors, with hERG inhibition properties that mitigate cardiovascular risks. Demonstrating significant antipsychotic efficacy in the MK-801-induced mouse model, this compound holds potential for psychosis research.

Remlifanserin is a potent inverse agonist of the serotonin receptor (5-HT2A).

Avitriptan is a 5-HT1B/1D receptor agonist with pKi values of 7.44 for 5-HT1Brat, 7.68 for 5-HT1Bhuman, and 8.36 for 5-HT1Dhuman. It can induce contraction in isolated coronary arteries and is used for the treatment of migraines.

DSP-1053: Benzylpiperidine-based, potent SERT inhibitor (Ki=1.02nM), partial 5-HT1A receptor agonist (Ki=5.05nM), antidepressant.

SB 258741 hydrochloride is a potent antagonist of the 5-HT 7 receptor, designed specifically for studying schizophrenia [1].

SEP-363856 (SEP-856) mesylate is an orally active compound that acts as an agonist for both TAAR1 and 5-HT1A receptors. This compound exhibits antipsychotic activity in the central nervous system and has potential for the study of schizophrenia.

5-HT2A receptor agonist-7 (517) functions as a modulator of the 5-HT2A receptor, with an EC50 value of less than 100 nM.

25C-NBF hydrochloride is an agonist of 5-HT receptors, specifically activating 5-HT2A and 5-HT2C receptors, with an EC50 of approximately 0.3 μM.

Jimscaline (compound R-(-)2) is a 5-HT2A agonist and a mescaline analogue, used in neuroscience research.

AAZ-A 154 hydrobromide is a selective, competitive, non-hallucinogenic 5-HT2AR antagonist. It promotes neuronal growth in rodents and yields enduring beneficial behavioral effects.

CTW0404 is an effective positive allosteric modulator (PAM) of the 5-HT receptor, with promising implications for research into neuropsychiatric disorders.

5-HT2A receptor agonist-8 (compound 8) is a potent 5-HT2A receptor agonist with an EC50 of 0.6784 nM. It is suitable for research related to depression and bipolar disorder.