Thioridazine, an antagonist of the dopamine receptor D2 family proteins, exhibits potent anti-psychotic and anti-anxiety activities. Thioridazine is also a potent inhibitor of PI3K-Akt-mTOR signaling pathways with anti-angiogenic effect. Thioridazine shows antiproliferative and apoptosis induction effects in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs)[1][2][3][4].
(R)-Viloxazine hydrochloride is a less active R-isomer of Viloxazine hydrochloride. Viloxazine hydrochloride is an effective antidepressant agent[1].
Quetiapine-d8 fumarate is the deuterium labeled Quetiapine. Quetiapine is a 5-HT receptors agonist with a pEC50 of 4.77 for human 5-HT1A receptor. Quetiapine is a dopamine receptor antagonist with a pIC50 of 6.33 for human D2 receptor. Quetiapine has moderate to high affinity for the human D2, HT1A, 5-HT2A, 5-HT2C receptor with pKis of 7.25, 5.74, 7.54, 5.55. Antidepressant and anxiolytic effects[1][2].
Scopolamine is a high affinity (nM) muscarinic antagonist. 5-HT3 receptor-responses are reversibly inhibited by Scopolamine with an IC50 of 2.09 μM.
NAN-190 hydrobromide is a serotonin receptor 5-HT antagonist. NAN-190 is a selective antagonist of 5-HT1A.Target: 5-HT in vitro: NAN-190 is a 5-HT1A antagonist. [3] NAN-190 is a selective antagonist of 5-HT1A. [1]in vivo: NAN-190 (0.5 mg/kg, ip), as a 5-HT1A receptor antagonist, is injected concomitantly with the effective dose of fluoxetine. NAN-190 (5-HT1A receptor antagonist) reverses the catalepsy-improving effect of fluoxetine in 6-OHDA lesioned rats. [2]
F-15599 is a highly selective G-protein biased 5-HT1A receptor agonist, with Ki of 3.4 nM.
Dolasetron Mesylate (MDL-73147) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy.
Agomelatine hydrochloride is a antidepressant, which is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. IC50 value: 6.2 (pKi, 5-HT2c); 6.6 (pKi, 5-HT2b)Target: 5-HT 2c receptor Agomelatine hydrochloride is an antidepressant drug. It is classified as a norepinephrine-dopamine disinhibitor (NDDI) due to its antagonism of the 5-HT2C receptor. Activation of 5-HT2C receptors by serotonin inhibits dopamine and norepinephrine release. Antagonism of 5-HT2C results in an enhancement of DA and NE release and activity of frontocortical dopaminergic and adrenergic pathways [1]. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kgagomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly [2].Clinical indications: Depression; Obsessive compulsive disorderFDA Approved Date: October 2011Toxicity: Hyperhidrosis; Abdominal pain; Nausea; Vomiting; Diarrhoea; Constipation; Back pain; Fatigue
SB 258719 is a selective 5-HT7 receptor antagonist with a pKi of 7.5.
CP-809101 Hcl is a potent and selective 5-HT2C receptor agonist with pEC50 of 9.96/7.19/6.81 for human 5-HT2C/5-HT2B/5-HT2A receptors respectively. IC50 Value: 9.96(pEC50 for 5-HT2C); 7.19(pEC50 for 5-HT2B); 6.81(pEC50 for 5-HT2A)Target: 5-HT2C ReceptorCP-809101 is a potent, functionally selective 5-HT2C agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT2C agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809101 dose-dependently inhibited conditioned avoidance responding (CAR, ED50 = 4.8 mg/kg, sc). CP-809101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED50 values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT2C agonist, CP-809101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness.
Renzapride (BRL 24924), a substituted benzamide, is a full 5-HT4 receptor agonist with a Ki value of 115 nM. Renzapride (BRL 24924) is also a 5HT2b and 5HT3 receptor antagonist[1]. Renzapride could be used for constipation predominant irritable bowel syndrome (C-IBS) study[2].
Idalopirdine (Lu AE58054) is a potent and selective 5-HT6 receptor antagonist with a Ki of 0.83 nM.
Clozapine N-oxide (CNO) is a major metabolite of the anti-psychotic drug clozapine. Clozapine N-oxide is a agonist for the chemogenetic Designer Receptors Exclusively Activated by Designer Drug (DREADD) system.
Frovatriptan succinate ((R)-Frovatriptan succinate) is a potent, high affinity, selective and orally active 5-HT1B (pK50 of 8.2) and 5-HT1D receptor agonist. Frovatriptan succinate exhibits >10-fold selectivity for 5-HT1B and 5-HT1D over 5-HT1A, 5-HT1F, and 5-HT7 and >1000-fold selectivity over other 5-HT, dopamine, histamine H1, and α1-adrenoceptor. Frovatriptan succinate has the potential for migraine research[1][2].
Setiptiline-d3 (Org-8282-d3) is the deuterium labeled Setiptiline. Setiptiline (Org-8282) is a serotonin receptor antagonist. Setiptiline is a tetracyclic antidepressant (TeCA) which acts as a noradrenergic and specific serotonergic antidepressant (NaSSA). Setiptiline acts as a norepinephrine reuptake inhibitor, α2-adrenergic receptor antagonist, and serotonin receptor antagonist, likely at the 5-HT2A, 5-HT2C, and/or 5-HT3 subtypes, as well as an H1 receptor inverse agonist/antihistamine[1][2].
Asenapine maleate, an antipsychotic, is a 5-HT (1A, 1B, 2A, 2B, 2C, 5A, 6, 7) and Dopamine (D2, D3, D4) receptor antagonist with Ki values of 0.03-4.0 nM for 5-HT and 1.3, 0.42, 1.1 nM for Dopamine receptor, respectively.
(-)-Penbutolol ((S)-Penbutolol) is a potent β-adrenoceptor and 5-HT receptor antagonist with Ki values of 11.6 nM and 11.9 nM for 5-HT in rat cornu ammonis 1 (CA1) and human CA3. (-)-Penbutolol can increase hippocampal 5-HT output[1][2].
Methiothepin maleate is a potent and non-selective 5-HT2 receptor antagonist, with pKds of 7.10 (5-HT1A), 7.28 (5HT1B), 7.56 (5HT1C), 6.99 (5HT1D), 7.0 (5-HT5A), 7.8 (5-HT5B), 8.74 (5-HT6), and 8.99 (5-HT7), and pKis of 8.50 (5HT2A), 8.68 (5HT2B), and 8.35 (5HT2C).
Relenopride (YKP10811) hydrochloride is a specific and selective 5-HT4 receptor agonist (Ki=4.96 nM). Relenopride hydrochloride has 120-fold and 6-fold lower affinity, respectively, for 5-HT2A (Ki=600 nM) and 5-HT2B receptors (Ki=31 nM) than for 5-HT4. Relenopride hydrochloride increases gastrointestinal (GI) motility[1][2].
Belaperidone (LU-111995), a 5-HT2A receptor inhibitor, possesses antidopaminergic and antiserotonergic effects[1].
SB 258719 (hydrochloride) is a selective 5-HT7 receptor antagonist displayed high affnity (pKi=7.5) for the receptor. SB-258719 (hydrochloride) can be used for the research of cancer and neurological diseases[1][2].
Xanthotoxol is a biologically active linear furocoumarin, shows strong pharmacological activities as anti-inflammatory, antioxidant, 5-HT antagonistic, and neuroprotective effects.
WAY-100635 maleate is a potent and selective 5-hydroxytryptamine1A antagonist with an IC50 of 0.95 ± 0.12 nM for 5-HT.IC50 Value: 0.95 nMTarget: 5-HT Receptorin vitro: WAY 100635 has an IC50 of 1.35 nM and is > 100-fold selective for the 5-HT1A site relative to a range of other CNS receptors. The Bmax of [3H]WAY 100635 specific binding is consistently 50-60% greater than that of the agonist radioligand, [3H]8-OH-DPAT. Mn2+, but not guanine nucleotides, inhibits [3H]WAY 100635-specific binding. WAY 100635 has no 5-HT1A receptor agonist actions, but dose-dependently blocks the effects of agonists at both the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-HT1A receptor locates on dorsal raphe 5-HT neurones. [3H]WAY 100635 has a Kd of approximately 2.5 nM. In the isolated guinea-pig ileum WAY 100635 is a potent and, at high concentrations, an insurmountable antagonist of the 5-HT1A receptor agonist action of 5-carboxamidotryptamine, with an apparent pA2 value (at 0.3 nM) of 9.71. in vivo: WAY 100635 blocks the inhibitory action of 8-OH-DPAT on dorsal raphe neuronal firing in the anaesthetised rat at doses which has no inhibitory action per se. In behavioural models, WAY 100635 itself induces no overt behavioural changes but potently antagonises the behavioural syndrome induced by 8-OH-DPAT in the rat and guinea-pig (minimum effective dose = 0.003 mg/kg s.c. and ID50 = 0.01 mg/kg s.c., respectively). WAY 100635 also blocks the hypothermia induced by 8-OH-DPAT in the mouse and rat with ID50 values of 0.01 mg/kg s.c.
Risperidone hydrochloride is a serotonin 5-HT2 receptor blocker and a potent dopamine D2 receptor antagonist, with Kis of 0.16, 1.4 nM for 5-HT2 and D2 receptor, respectively.
(Rac)-SEP-363856 is the racemate of SEP-363856. SEP-363856（SEP-856）, an orally active and CNS active psychotropic agent with a unique, non-D2/5-HT2A mechanism of action, exerts its antipsychotic-like effects. SEP-363856 （SEP-856） has the potential for the treatment of schizophrenia[1].
SB 206553 is a potent and selective 5-HT2B/5-HT2C receptor antagonist with pA2 of 8.89 for rat 5-HT2B, pKi of 7.92 for human 5-HT2C, displays >80-fold selectivity over other 5-HT receptor subtypes; exhibits anxiolytic-like properties both in vitro and in vivo. Anxiety Discontinued
TG6-10-1 is an EP2 antagonist, shows low-nanomolar antagonist activity against only EP2, >300-fold selectivity over human EP3, EP4, and IP receptors, 100-fold selectivity over EP1 receptors. IC50 value: 7.5 μMTarget: serotonin 5-HT2B receptorin vitro: TG6-10-1, an analog of TG4-155 (a prostaglandin receptor EP2 antagonist, with a relatively short plasma half-life (0.6 h) and low brain:plasma ratio (0.3) after systemic administration in mice), which has a superior pharmacokinetic profile making it suitable for more extensive testing. TG6-10-1 had negligible effect on a panel of 40 enzymes, ion channels, receptors, and neurotransmitter transporters (IC50s > 10 μM), except that TG6-10-1 weakly inhibited the serotonin 5-hydroxytryptamine 2B (5-HT2B) receptor with IC50 = 7.5 μM. At a high concentration (10 μM), TG6-10-1 had little or no effect on the enzymatic activity of COX-1 (7% inhibition) and COX-2 (14% inhibition), and inhibited the leukotriene B4 (LTB4) receptor BLT1 by 1% .EP2 receptor activation by PGE2 stimulates adenylate cyclase to elevate cytoplasmic cAMP level. TG6-10-1 has a competitive mechanism of antagonism of the EP2 receptor with an equilibrium dissociation constant for the antagonist-receptor complex (KB) of 17.8 nM.in vivo: TG6-10-1 displayed a plasma half-life of 1.6 h and a brain:plasma ratio of 1.6 after systemic administration (5 mg/kg, i.p.) in mice. A significant increase in survival was observed in post-SE mice that received TG6-10-1 compared with those in the vehicle group. Administration of TG6-10-1 improved 1-wk survival from 60 to 90% after SE.
Thioridazine is an antipsychotic drug, used in the treatment of schizophrenia and psychosis, shows D4 selectivity or serotonin antagonism.
Spiperone hydrochloride (Spiroperidol hydrochloride) is a selective dopamine D2 receptor (Ki values of 0.06 nM, 0.6 nM, 0.08 nM, ~350 nM, ~3500 nM for D2, D3, D4, D1 and D5 receptors, respectively) and 5-HT2A/5-HT1A receptor (Kis of 1 nM/49 nM) antagonist. Spiperone hydrochloride is also a selective α1B-adrenoceptor antagonist. Spiperone hydrochloride activates calcium-activated chloride channel (CaCC). Antipsychotic and anti-inflammatory activities[1][2][3][4][5].
LP 12 hydrochloride (compound 21) is a potent and selective 5-HT7 receptor agonist with a Ki of 0.13 nM. LP 12 hydrochloride displays selectivity for 5-HT7 over D2, 5-HT1A and 5-HT2A receptors (Ki values are 224 nM, 60.9 nM and >1000 nM, respectively)[1].