Serotonin Transporter Inhibitor

Amitriptyline hydrochloride is an orally active tricyclic antidepressant (TCA). Amitriptyline hydrochloride mainly exerts its antidepressant effect by blocking SERT (K_i = 3.45 nM) and NET (K_i = 13.3 nM), thereby increasing the concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the synaptic cleft. Amitriptyline hydrochloride is also an agonist at α2A and TrkA/TrkB receptors, thereby exerting analgesic and neurotrophic activities (inhibiting cell apoptosis). Amitriptyline hydrochloride can reduce inflammation, angiogenesis and fibrosis. Amitriptyline hydrochloride binds to DAT (with K_i = 2.58 μM). Amitriptyline hydrochloride has high affinity for a series of receptors and can antagonize muscarinic cholinergic receptors (M1/M2/M3/M4/M5 receptors) (K_i = 11-24 nM), H1 receptors (K_i = 0.5-1.1 nM), adrenergic α1 receptors (K_i = 4.4 nM), etc., resulting in a series of side effects. Amitriptyline hydrochloride can block sodium channels and hERG potassium channel (IC₅₀ = 4.78 μM) and it has cardiotoxicity.

Vilazodone Hydrochloride (EMD 68843 Hydrochloride) is a serotonin transporter (SER) inhibitor and 5-HT_1A receptor partial agonist.

Atomoxetine (Tomoxetine) hydrochloride is a selective noradrenaline reuptake inhibitor with K_i values of 5 nM, 77 nM and 1451 nM for norepinephrine (NE), serotonin (5-HT) and dopamine (DA) transporters, respectively. Atomoxetine hydrochloride is a potent Na⁺ channels (VGSCs) blocker. Atomoxetine hydrochloride can be used for attention-deficit hyperactivity disorder (ADHD) research.

Clomipramine (Chlorimipramine) hydrochloride is a potent 5-HT reuptake blocker with the IC₅₀ value of 1.5 nM. Clomipramine hydrochloride is a tricyclic antidepressant that can be used for the research of depression and obsessive compulsive disorder (OCD).

Fluvoxamine maleate (DU-23000 maleate) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor.

Venlafaxine hydrochloride (Wy 45030 hydrochloride) is an orally active, potent serotonin (5-HT)/norepinephrine (NE) reuptake dual inhibitor. Venlafaxine is an antidepressant.

Citalopram hydrobromide is a selective serotonin reuptake inhibitor (SSRI), with blood-brain barrier permeability. Citalopram hydrobromide inhibits 5-HT uptake into synaptosomes with an IC₅₀ of 1.8 nM. Citalopram hydrobromideinhibits the 5-HT uptake in rabbit blood platelets with an IC₅₀ of 14 nM. Antidepressant effect.

Duloxetine is a serotonin-norepinephrine reuptake inhibitor with a K_i of 4.6 nM, used for treatment of major depressive disorder and generalized anxiety disorder (GAD).

Pseudoisocyanine iodide (1,1'-Diethyl-2,2'-cyanine iodide) is an inhibitor of organic cation transporters (OCT1, OCT2, OCT3) and plasma membrane monoamine transporter (PMAT). Pseudoisocyanine iodide has antidepressant activity.

Milnacipran hydrochloride is an orally active Serotonin (HY-B1473A) and Norepinephrine (HY-13715) reuptake inhibitor. Milnacipran hydrochloride inhibits monoamine transporters, especially the norepinephrine transporter and the serotonin transporter (K_i values of 31 and 8.5 nM, respectively). Milnacipran hydrochloride inhibits pERK1/2 activation. Milnacipran hydrochloride has antidepressant, anxiolytic and analgesic properties. Milnacipran hydrochloride inhibits biting behavior in mice. Milnacipran hydrochloride can be used in the study of major depressive disorder, anxiety disorders, and neuropathic pain (e.g., fibromyalgia).

Tesofensine (NS-2330) is a triple monoamine reuptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine (DA; IC₅₀=6.5 nM), norepinephrine (NE;IC₅₀=1.7 nM), and serotonin (5-HT;IC₅₀=11 nM), and with potentials as an anti-obesity agent. Tesofensine is a CNS acting anti-obesity agent.

Dasotraline hydrochloride (SEP-225289 hydrochloride) is a triple reuptake inhibitor that blocks dopamine, norepinephrine, and serotonin transporters with IC₅₀ values of 4, 6, and 11 nM, respectively.

Desvenlafaxine, the succinate salt form of the isolated major active metabolite of Venlafaxine (HY-B0196), is an orally active and BBB penetrated 5-HT and norepinephrine reuptake inhibitor, with IC₅₀ values of 47.3 nM and 531.3 nM for hSERT and hNET, respectively. Desvenlafaxine shows weak binding affinity (62% inhibition at 100 μM) at the human dopamine (DA) transporter.

PH-064 (BIM-46187) is an orally active inhibitor of the heterotrimeric G-protein complex. PH-064 inhibits SERT activity and attenuates shear stress-induced Akt phosphorylation. PH-064 has potent anti-hyperalgesia activity. PH-064 inhibits G protein-coupled receptor-dependent tumorigenesis. PH-064 can be used in the study of pain (e.g., inflammatory pain, neuropathic pain), GPCR-dependent tumors, and inflammatory lung injury.

Paroxetine (BRL29060) hydrochloride hemihydrate is an orally active and selective serotonin reuptake inhibitor (SSRI) and apoptosis inducer with blood-brain barrier permeability. Paroxetine hydrochloride hemihydrate inhibits nitric oxide synthase and CYP2D6, induces desensitization of 5-HT1A/1B/1D autoreceptors, downregulates 5-HT2 receptors, and promotes the production of inflammatory cytokines. Paroxetine hydrochloride hemihydrate is a weak norepinephrine (NE) uptake inhibitor and possesses antitumor activity. Paroxetine hydrochloride hemihydrate is widely used in research concerning depression, obsessive-compulsive disorder, panic disorder, social phobia, generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, hot flashes, and related conditions.

Centanafadine (hydrochloride) is dual norepinephrine (NE)/dopamine (DA) transporter inhibitor, also inhibits serotonin transporter, with IC₅₀s of 6 nM, 38 nM and 83 nM for human NE, DA and serotonin transporter , respectively.

Norquetiapine ( N-Desalkylauetiapine), a metabolite of Quetiapine (HY-14544), is a selective HCN1 channel inhibitor, with an IC₅₀ of 13.9 μM. Norquetiapine selectively inhibits noradrenaline reuptake, is a partial 5-HT_1A (K_i = 45 nM) receptor agonist, and acts as an antagonist at presynapticα2 (K_i = 237 nM), 5-HT_2C(K_i = 107 nM), and 5-HT₇ (K_i = 76 nM) receptors. Norquetiapine blocks the human cardiac sodium channel Nav1.5 in a state-dependent manner. Norquetiapine shows partial anti-inflammatory effects in LPS (HY-D1056) injected C57BL/6 mice. Norquetiapine can be used for the study of depression and inflammation.

Desvenlafaxine succinate hydrate, the succinate salt form of the isolated major active metabolite of Venlafaxine (HY-B0196), is an orally active and BBB penetrated 5-HT and norepinephrine reuptake inhibitor, with IC₅₀ values of 47.3 nM and 531.3 nM for hSERT and hNET, respectively. Desvenlafaxine succinate hydrate shows weak binding affinity (62% inhibition at 100 μM) at the human dopamine (DA) transporter.

Dapoxetine (LY-210448) hydrochloride is an orally active and selective serotonin reuptake inhibitor (SSRI). Dapoxetine hydrochloride can be used for the research of premature ejaculation (PE).

SERT-IN-2 is a potent SERT inhibitor (IC₅₀=0.58 nM) with promising anti-depression efficacy. SERT-IN-2 shows good bioavailability of 83.28% in rats. SERT-IN-2 can cross the blood-brain barrier.