SB269970 is a 5-HT7 receptor antagonist with pKi of 8.3, exhibits >50-fold selectivity against other receptors.IC50 Value: 8.3 (pKi for 5-HT7) [1]Target: 5-HT7 receptorin vitro: 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes (pEC(50) of 8.4+/-0.2) was inhibited by SB-269970-A (0.3 microM) with a pK(B) (8.3+/-0.1) in good agreement with its antagonist potency at the human cloned 5-HT(7(a)) receptor and its binding affinity at guinea-pig cortical membranes. 5-HT(7) receptor mRNA was highly expressed in human hypothalamus, amygdala, thalamus, hippocampus and testis [1]. Cortical slices were loaded with [(3)H]-5-HT and release was evoked by electrical stimulation. 5-CT inhibited the evoked release of [(3)H]-5-HT in a concentration-dependent manner. SB-269970 had no significant effect on [(3)H]-5-HT release while the 5-HT(1B) receptor antagonist, SB-224289 significantly potentiated [(3)H]-5-HT release. In addition, SB-269970 was unable to attenuate the 5-CT-induced inhibition of release while SB-224289 produced a rightward shift of the 5-CT response, generating estimated pK(B) values of 7.8 and 7.6 at the guinea-pig and rat terminal 5-HT autoreceptors respectively [2].in vivo: Acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions [3]. Pretreatment with a dose of SB-269970 (0.5 mM) that significantly affects sleep variables antagonized the LP-44 (2.5 mM)-induced suppression of REMS and of the number of REM periods [4].Toxicity: N/AClinical trial: N/A
Pimavanserin is a selective inverse agonist of the 5-HT2A receptor with pIC50 and pKd of 8.73 and 9.3, respectively.
PU02, a derivative of 6-MP (HY-13677), is a negative allosteric modulator (NAM) of 5-HT3 receptor, with IC50 values of 0.36 and 0.73 μM in HEK293 cells transfected with human 5-HT3A and 5-HT3AB receptors respectively[1][2].
Tandospirone(SM-3997) is a potent and selective 5-HT1A receptor partial agonist (Ki = 27 nM) that displays selectivity over SR-2, SR-1C, α1, α2, D1 and D2 receptors (Ki values ranging from 1300-41000 nM). IC50 Value: 27±5 nM(Ki) [1]Target: 5-HT1Ain vitro: Tandospirone is most potent at the 5-HT1A receptor, displaying a Ki value of 27 +/- 5 nM. The agent is approximately two to three orders of magnitude less potent at 5-HT2, 5-HT1C, alpha 1-adrenergic, alpha 2-adrenergic, and dopamine D1 and D2 receptors (Ki values ranging from 1300 to 41000 nM). Tandospirone is essentially inactive at 5-HT1B receptors; 5-HT uptake sites; beta-adrenergic, muscarinic cholinergic, and benzodiazepine receptors [1]. 3H-SM-3997 bound rapidly, reversibly and in a saturable manner with high affinity to rat brain hippocampal membranes (Kd = 9.4 nM, Bmax = 213 fmol/mg protein) [2]. in vivo: Chronic treatment with tandospirone, at 0.2 and 1.0mg/kg/day, but not 2.0mg/kg/day, attenuated footshock stress-induced eLAC elevation in the mPFC [3]. Rats were acutely administered tandospirone (0, 0.1, and 1 mg/kg, i.p.). Tandospirone decreased the number of premature responses, an index of impulsive action, in a dose-dependent manner [4].Toxicity: It is not believed to be addictive but it is known to produce mild withdrawal effects (e.g. anorexia) after abrupt discontinuation.
GR 113808 is a potent and highly selective 5-HT4 receptor antagonist (pKb= 8.8). GR 113808 shows 300-fold selectivity over 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT3 receptors[1].
Asenapine maleate is a 5-HT (1A, 1B, 2A, 2B, 2C, 5A, 6, 7) and D2 antagonist with Ki values of 0.03-4.0 nM, 1.3nM, respectively, and an antipsychotic.
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].
5-HT2A&5-HT2C agonist-1 (Example 2) is a 5-HT2A & 5-HT2C agonist, with IC50s of 196 nM and 0.9 nM respectively. 5-HT2A&5-HT2C agonist-1 can be used for research of depression, alcoholism, tobacco and cocaine addiction, inflammation, cluster headache, PTSD, seizure disorders and other CNS disorders[1].
Dothiepin (Dosulepin; Dothep) is an antidepressant agent with sedative/anxiolytic activity. Dothiepin is an inhibitor preferring of noradrenaline uptake than serotonin uptake. Dothiepin facilitates noradrenergic neurotransmission via inhibiting the neuronal uptake. Dothiepin is also an antagonist of histamine H1-receptor without cardiotoxicity. Dothiepin exhibits significant analgesic activity in psychogenic facial pain，idiopathic fibromyalgia syndrome or rheumatoid arthritis[1].
Desmethyl cariprazine is an active metabolite of Cariprazine[1]. Cariprazine, an antipsychotic drug candidate, exhibits high affinity for the D3 (Ki=0.085 nM) and D2 (0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (2.6 nM)[2].
NAS-181 is a potent and selective rat 5-hydroxytryptamine1B (r5-HT1B) antagonist with an Ki value of 47 nM. NAS-181 increases the 5-HTP accumulation in rat brain regions[1].
Tropanserin is a serotoninergic active compound, as well as a 5HT3 receptor antagonist. Tropanserin modulates Cardio-respiratory reflex effects of an exogenous serotonin challenge[1].
Myristicine act as a serotonin receptor antagonist, a weak monamine oxidase (MAO) inhibitor. Myristicine is the main component of nutmeg essential oil from Myristica fragrans Houtt. Myristicine abuse produce hallucinogenic effects, organ damage, deliriumand others[1].
Wf-516 is an inhibitor of 5-HT reuptake, and an antagonist of 5-HT1A and 5-HT2A receptors, with Ki of 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively, and has potent antidepressant activity.
LP44 (hydrochloride) is a selective 5-HT7 agonist with Ki of 0.22 nM. LP44 (hydrochloride) induces hypothermic effect in a dose-dependent manner by intracerebroventricular injection. LP44 (hydrochloride) not causes considerable hypothermic response by intraperitoneal administration[1].
Dehydro Palonosetron (RS 42358-197) is a potent, seslective and orally active 5-HT3 receptor antagonist. Dehydro Palonosetron has no effect on the activities of 5-HT1 receptors, 5-HT2 receptors or 5-HT4 receptors[1].
Agomelatine D6 (S-20098 D6) is deuterium labeled Agomelatine. Agomelatine is a specific agonist of MT1 and MT2 receptors[1] .
SB 243213 hydrochloride is an orally active, selective and high-affinity 5-hydroxytryptamine (5-HT)2C receptor antagonist with a pKi of 9.37 and a pKb of 9.8 for human 5-HT2C receptor. SB 243213 hydrochloride has improved anxiolytic profile and has the potential for schizophrenia and motor disorders[1].
PCPA methyl ester hydrochloride (4-Chloro-DL-phenylalanine methyl ester hydrochloride), a reversible tryptophan hydroxylase inhibitor, is a serotonin (5-HT) synthesis inhibitor. PCPA methyl ester hydrochloride crosses the blood brain barrier and reduces 5-HT central availability[1][2].
Scopolamine hydrobromide is a high affinity (nM) muscarinic antagonist. 5-HT3 receptor-responses are reversibly inhibited by Scopolamine with an IC50 of 2.09 μM.
Temanogrel is a highly selective 5-HT2A receptor antagonist with a Ki of 4.9 nM.
Granisetron Hcl(BRL 43694A) is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy.IC50 Value: 17uM (GR reduced 5-HT-evoked contractions) [1]Target: 5-HT3 receptorin vitro: In rat forestomach GR reduced 5-HT-evoked contractions at IC50 17 /- 6 uM. In isolated rabbit heart, GR 0.003-0.03 nM dose-dependently reduced s-HT tachycardia; at high levels GR reduced submaximal and maximal responses to 5-HT [1].in vivo: Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. Granisetron increased PGE(2) level at a lower dose (50 microg/pouch) but higher doses (100 and 200 microg/pouch) inhibited the release. At the same time, TNFalpha production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion [2]. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation [3].Clinical trial: Effect of External Heat on a Transdermal Granisetron Patch in Pharmacokinetics (PK) of Healthy Subjects. Phase 1
5-HT2C agonist-3 ((+)-19) is a selective 5-HT2C agonist (EC50: 24 nM, Ki: 78 nM). 5-HT2C agonist-3 has antipsychotic drug-like activity. 5-HT2C agonist-3 blocks Amphetamine-induced hyperactivity[1].
WAY 163909 is a potent and selective 5-HT(2C) receptor agonist with a Ki of 10.5±1.1 nM.
Bemesetron (MDL 72222) is a selective 5-HT3 receptor antagonist with an IC50 of 0.33 nM[1]. Neuroprotective effects[2].
Valerenic acid ((-)-Valerenic Acid), a sesquiterpenoid, is an orally active positive allosteric modulator of GABAA receptors. Valerenic acid is also a partial agonist of the 5-HT5a receptor. Valerenic acid mediates anxiolytic activity via GABAA receptors containing the β3 subunit. Valerenic acid also exhibits potent antioxidant properties[1][2][3].
3,4-Dihydro Naratriptan is a serotonin 5-HT1-receptor agonist. 3,4-Dihydro Naratriptan exhibits selective vasoconstrictor activity. 3,4-Dihydro Naratriptan can be used for migraine diseases research[1].
ST1936 is a selective, nanomolar affinity 5-HT6 receptor agonist with Ki values of 13 nM, 168 nM and 245 nM for human 5-HT6, 5-HT7 and 5-HT2B receptors, respectively. ST1936 also shows moderate affinity (Ki of 300 nM) for human and rat α2 adrenergic receptor[1].
GR-46611 is a 5-HT1D receptor agonist. GR-46611 can be used in the research of bladder hyperactivity, leukemia[1][3].
Ziprasidone amino acid (Ziprasidone Impurity C) is an impurity of Ziprasidone. Ziprasidone is a combined 5-HT (serotonin) and dopamine receptor antagonist. Ziprasidone exhibits potent effects of antipsychotic activity [1].