antidepressant-like

TAK-137 is a novel AMPA receptor potentiator with little agonistic effect, producing antidepressant-like effect without causing psychotomimetic effects.

OPC-14523 hydrochloride is an orally active sigma and 5-HT1A receptor agonist with antidepressant-like activity, showing high affinity for the sigma receptor σ1 2 (IC50=47 56 nM), the 5-HT1A receptor (IC50=2.3 nM), and the 5-HT transporter (IC50=80 nM).

SNC 80 (NIH 10815) is a potent, highly selective and non-peptide δ-opioid receptor agonist, Ki = 1.78 nM, IC50 = 2.73 nM. SNC80 also selectively activates μ-δ heteromer in HEK293 cells with an EC50 of 52.8 nM. SNC80 shows antinociceptive, antihyperalgesic and antidepressant‐like effects. SNC80 has the potential for multiple headache disorders treatment.

Purpurin (Verantin) was a reversible and competitive inhibitor of MAO-A with a Ki value of 0.422μM. it exhibits anti-angiogenic, antifungal, antibiotic, and antioxidative activities.

1. trans-Cinnamaldehyde (Phenylacrolein) exhibits excellent anti-inflammatory activities and antidepressant-like effects in stressed mid-aged rats as a COX-2 inhibitor. 2. Cinnamic aldehyde induces apoptosis of CML cells in vitro, down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms. 3. Cinnamic aldehyde and cinnamic acid are cardioprotective in a rat model of ischemic myocardial injury, the mechanism is related to anti-oxidative and anti-inflammatory properties.

(-)-Perillaldehyde shows antibacterial activity.

F13714 fumarate is a selective 5-HT1A receptor-biased agonist with antidepressant-like properties after a single dose in a mouse model of chronic mild stress.

1. Orientin (Luteolin-8-glucoside) may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 2. Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. 3. Orientin has neuroprotection effect by the intracellular mediation of caspase activity; may alleviate cognitive deficits and oxidative stress in AD mice; can exert antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity.

Carbetocin is an obstetric drug used to control postpartum hemorrhage and bleeding after giving birth.

URB-597 (FAAH Inhibitor II) is an effective, orally bioavailable FAAH inhibitor (IC50: 4.6 nM), and no effect on other cannabinoid-related targets.

Jatrorrhizine (neprotin) is a protoberberine alkaloid isolated from Enantia chlorantha (Annonaceae) and other species. It was found to have antimicrobial and antifungal activity. It binds and noncompetitively inhibits monoamine oxidase (IC50 4 micromolar for MAO-A and 62 for MAO-B).

Sibiricose A5 is a lactate dehydrogenase inhibitor, it displays antidepressant-like, and antioxidant actions. Sibiricose A5 can protect PC12 cells damage induced by P. tenuifolia.

TAK-653, a selective positive allosteric modulator (PAM) of AMPA receptors exhibiting minimal agonistic activity, elicits an antidepressant-like response while maintaining a favorable safety profile in rat models.

FCPR03 is a selective inhibitor of phosphodiesterase 4 (PDE4) with IC50s of 31 nM, 47 nM, and 60 nM for PDE4B1, PDE4D7, and PDE4 catalytic domain, respectively. FCPR03 has neuroprotective, anti-inflammatory, and antidepressant-like effects.

Luzindole (N-0774) is a selective melatonin receptor antagonist that inhibits experimental autoimmune encephalomyelitis and exhibits antidepressant-like activity. It preferentially targets MT2 (Mel1b) over MT1 (Mel1a), with Ki values of 10.2 nM for human MT2 and 158 nM for MT1.

p-MPPI hydrochloride is a selective 5-HT1A receptor antagonist with antidepressant and anxiolytic-like effects.

4-Hydroxyisoleucine (4-Hydroxy-L-isoleucine) has antidepressant-like, antidyslipidemic, and antihyperglycemic effects. It displays an insulinotropic activity.

SF 11 is a potent, brain-penetrant neuropeptide Y Y2 receptor antagonist with an IC50 of 199 nM, exhibiting antidepressant-like activity.

TRIM (1-(2-Trifluoromethylphenyl)imidazole) is an inhibitor of nNOS.

BU 224 hydrochloride is a selective imidazoline I(2) binding site ligand and has antinociceptive and antidepressant-like activities.

1. Sibiricose A6 displays antidepressant-like action, it may prevent or relieve depression. 2. Sibiricose A6 shows potent antioxidant activity.

Bacopaside I is a saponin isolated from Bacopa monniera. Bacopaside I is a modulator of Aquaporin-1 channel, has neuroprotective functions, it has anti-Alzheimer's disease, it ameliorates cognitive impairment in APP PS1 mice via immune-mediated clearance of α2-amyloid,exbibits antioxidant properties and free radical scavenging capacity and exerts antidepressant-like effect.

CX 717 is a positive allosteric modulator of the AMPA receptor with antidepressant-like effects and potential use in adult attention deficit hyperactivity disorder (ADHD) research [1] [2].

Tipepidine hydrochloride is a reversible inhibitor of dopamine (DA) D2 receptor-mediated GIRK currents (IDA(GIRK)) (IC50: 7.0 μM), with antidepressant-like effect.

Tyrosylleucine (Tyr-Leu, YL) TFA is a dipeptide compound with potent antidepressant-like activity and demonstrates effective modulation of depressive symptoms when administered orally.

ETAP, a dual inhibitor of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B), exhibits antidepressant-like effects and is utilized in the research of major depressive disorder [1].

NBI-31772 hydrate is a powerful inhibitor of the interaction between insulin-like growth factor (IGF) and IGF-binding proteins (IGFBPs). It acts as a nonpeptide ligand, effectively releasing bioactive IGF-I from the IGF-I/IGFBP-3 complex (Ki values for all six human subtypes range from 1-24 nM). This compound demonstrates significant anxiolytic and antidepressant-like effects [1] [2] [3].

LY3020371 hydrochloride exerts an antidepressant-like signature in vivo. LY3020371 hydrochloride is a potent, selective metabotropic glutamate 2/3 receptor (mGlu2/3) antagonist with Ki of 5.3 and 2.5 nM, potently blocks cAMP formation with IC50 of 16.2 nM.

Tofenacin (free base) is an antidepressant drug with a tricyclic-like structure. It acts as a serotonin-norepinephrine reuptake inhibitor, and based on its close relation to orphenadrine, may also possess anticholinergic and antihistamine properties. Tofenacin is also the major active metabolite of orphenadrine and likely plays a role in its beneficial effects against depressive symptoms seen in Parkinson's disease patients.

MGS-0039 is a group II metabotropic glutamate receptor (mgluR2/3) antagonist. Antidepressant-like action of group II mGlu receptor antagonists does not depend on serotonergic system activation. However, the AMPA receptor seems to play a key role in the an

Osanetant produces anxiolytic- and antidepressant-like effects. Osanetant is a selective NK3 receptor antagonist. It is researched for schizophrenia.

Fluoroethylnormemantine hydrochloride, a Memantine derivative, functions as an antagonist for the N-methyl-D-aspartate (NMDA) receptor. It can also serve as a positron emission tomography (PET) tracer, specifically as [18F]-Fluoroethylnormemantine hydrochloride. Notably, this compound displays a range of effects, including anti-amnesic, neuroprotective, antidepressant-like, and fear-attenuating properties.

Tianeptine metabolite MC5, an active derivative of the atypical antidepressant tianeptine produced through β-oxidation, exhibits selective G protein activation in bioluminescence resonance energy transfer (BRET) assays. Utilizing HEK293T cells expressing the human μ-opioid receptor (MOR) over the human δ-opioid receptor (DOR; EC50s = 0.454 and >100 µM, respectively), it demonstrates specificity. Moreover, this metabolite reduces immobility in wild-type mice during the forced swim test at a dose of 30 mg/kg, an effect not observed in MOR knockout mice, suggesting its antidepressant-like activity is MOR-dependent.

XAP044 is a mGlu7-selective antagonist which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm[1].

Rosavin (Rosavidin) has antidepressant and anxiolytic actions, helps balance all the neurotransmitters.

Jatrorrhizine chloride (Neprotine chloride) is a potent and orally active uptake-2 transporter inhibitor. It exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of the MAPK pathway in HT22 hippocampal neurons.

Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011). Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4 References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011).

SRA880 is a non-peptide antagonist of somatostatin sst1-receptor. SRA880 displayed significantly lower affinity for the other human recombinant somatostatin receptors ( pK(d) < or = 6.0). SRA880 shows a certain binding affinity to the human dopamine D4 re

SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer’s disease (AD) treatment.

Fluoroethylnormemantine, a derivative of Memantine, acts as an N-methyl-D-aspartate (NMDA) receptor antagonist and can function as a positron emission tomography (PET) tracer known as [18F]-fluoroethylnormemantine. This compound displays anti-amnesic, neuroprotective, antidepressant-like, and fear-attenuating properties.

Nemifitide diTFA (INN 00835 diTFA) is a synthetic pentapeptide that can cross the blood-brain barrier and acts as a potent antidepressant, similar to melanocyte suppressor factor (MIF).

CP 122721 hydrochloride is a potent and selective non-peptide (nonpeptide) neurokinin NK1 antagonist, demonstrating a pIC50 of 9.8 against the human NK1 receptor in IM-9 cells. It exhibits anxiolytic and antidepressant-like effects, as evidenced in studies [1] [2].

alpha-Asarone (trans-Asarone) is a psychoactive compound with antidepressant-like activity in mice.

Tenuifoliside A has anti-apoptotic , neuroprotective activity. And tenuifoliside A has anti-inflammatory effect, which is mediated by the inhibition of the NF-κB and MAPK pathways.

BW373U86 (SNC86), a δ-opioid receptor agonist, demonstrates potent activity with an IC50 value of 1.49 nM and has shown to exhibit antidepressant-like effects [1].

MTEP, a potent, non-competitive, and highly selective antagonist of mGluR5, exhibits an IC50 value of 5 nM and a K_i value of 16 nM. Demonstrating antidepressant and anxiolytic-like effects, MTEP is utilized in Parkinson's disease research.

(S)-Osanetant, the S-enantiomer of Osanetant (SR142801), is a selective NK3 receptor antagonist known for its anxiolytic- and antidepressant-like effects. It is currently under investigation for potential use in treating schizophrenia [1].

RU 43044 is a selective glucocorticoid receptor antagonist that has exhibited an antidepressant-like effect.