Schizophrenia

Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors. Glycine is orally active. Glycine inhibits the membrane aggregation of NINJ1 and prevents plasma membrane rupture during cell death. Glycine can be used to study cell protection, cancer, neurological diseases, and angiogenesis.

Clozapine (HF 1854) is an antipsychotic used for the research of schizophrenia. Clozapine has high affinity for a number of neuroreceptors. Clozapine is a potent antagonist of dopamine D2 with a K_i of 75 nM. Clozapine inhibits the muscarinic M1 receptor and serotonin 5HT2A receptor with K_is of 9.5 nM and 4 nM, respectively. Clozapine is also a potent and selective agonist at the muscarinic M4 receptor (EC₅₀=11 nM).

TP-10 is a selective PDE10A inhibitor with an IC₅₀ value of 0.8 nM. TP-10 shows an antioxidant activity with IC₅₀s of 31.72 and 16.04 μg/ml for DPPH and CUPRAC, respectively. TP-10 can be used for the research of neuropathy.

Pregnenolone monosulfate (3β-Hydroxy-5-pregnen-20-one monosulfate) is a powerful neurosteroid, the main precursor of various steroid hormones including steroid ketones. Pregnenolone monosulfate acts as a signaling-specific inhibitor of cannabinoid CB1 receptor, inhibits the effects of tetrahydrocannabinol (THC) that are mediated by the CB1 receptors. Pregnenolone monosulfate can protect the brain from cannabis intoxication. Pregnenolone monosulfate is also a TRPM3 channel activator, and also can weakly activate TRPM1 channels.

GSK239512 is a blood-brain barrier-permeable, orally active H3 receptor antagonist, with a human pK_i ranging from <5.5 to 9.92 and a murine pK_i ranging from 9.44 to 9.83. GSK239512 modulates cholinergic and monoaminergic neurotransmission, blocks the inhibitory feedback of H3 receptors, and increases the release of pro-cognitive neurotransmitters. GSK239512 induces oligodendrocyte precursor cell differentiation and restores myelin gene expression at the cellular level. GSK239512 reverses Scopolamine (HY-N0296)-induced memory deficits and improves recognition memory in animal models. GSK239512 can be used in research related to Alzheimer's disease, chronic traumatic encephalopathy, relapsing-remitting multiple sclerosis, and schizophrenia.

CPL500036 is an orally active, blood-brain barrier permeable phosphodiesterase 10A (PDE10A) inhibitor with IC₅₀ values of 1 nM (Reference 1) and 35 nM (Reference 2). CPL500036 acts as a negative allosteric modulator of the M2 muscarinic receptor with an IC₅₀ of 9.2 μM. CPL500036 alters cyclic nucleotide levels in basal ganglia circuits, inhibits the hydrolysis of cAMP and cGMP, and suppresses hERG potassium channel tail currents. CPL500036 induces catalepsy in rats and reverses injury-induced contralateral forelimb use impairment. CPL500036 can be used in research related to schizophrenia, Parkinson's disease, and levodopa-induced dyskinesia.

Octoclothepin (Clorotepine) is a D₂ dopamine receptor antagonist and 5-HT₂ serotonin receptor antagonist , with K_i values of 0.67 nM, 0.57 nM, and 0.19 nM for the dopamine D₂, 5-HT_2A, and 5-HT_2C receptors, respectively. Octoclothepin also binds to adrenergic receptors, with K_i values of 0.66 nM, 0.56 nM, and 0.77 nM for α_1a, α_1b, and α_1d, respectively. Octoclothepin can be used in schizophrenia research.

NK3R antagonist-2 (Compound 45) is a small-molecule antagonist of tachykinin NK3R, with an IC₅₀ of 1100 nM and a K_i of 1800 nM. NK3R antagonist-2 can be used in the research of schizophrenia.

MK-212 monohydrochloride (CPP monohydrochloride) is an orally active, blood-brain barrier permeable agonist of 5-HT₁C, 5-HT₂ and 5-HT₁A receptors. MK-212 monohydrochloride induces hyperthermia, nausea, arousal, irritability and restlessness, inhibits the elevation of plasma cortisol and prolactin, and reduces feelings of calmness and overall positive affect. MK-212 monohydrochloride mediates anxiety-like behaviors and motor inhibition. MK-212 monohydrochloride is applicable to research related to schizophrenia and anxiety disorders.

Molindone hydrochloride (EN-1733A) is an orally active and brain-penetrant dopamine D2/D5 receptor antagonist. Molindone hydrochloride shows antipsychotic and antidepressant-like activities. Molindone hydrochloride suppresses spontaneous locomotion, and antagonizes apomorphine-induced emesis. Molindone hydrochloride can be used for the research of neurological disease.

Levomepromazine maleate (Methotrimeprazine maleate) is an orally active antipsychotic compound and Ca²⁺ release inducer. Levomepromazine maleate inhibits SERCA pump and induces an increase in cytoplasmic Ca²⁺ levels. Levomepromazine maleate has antagonistic effects on a variety of neurotransmitter receptors, including dopamine, cholinergic, serotonin, and histamine receptors. Levomepromazine maleate can induce adaptive ER stress and autophagy. In addition, Levomepromazine maleate has antiviral, anti-inflammatory, neuroprotective and analgesic, sedative and anti-injurious activities. Levomepromazine maleate can be used in the study psychiatric disorders and relieving nausea and vomiting.

Unifiram (DM232) is a AMPA receptor activator and cognitive enhancer. Unifiram activates the AMPA-mediated neurotransmission system. Unifiram reverses NBQX-induced amnesia in the passive avoidance test in mice. Unifiram reverses the antagonistic effect of kynurenic acid on NMDA-mediated [³H]NA release in rat hippocampal slices. Unifiram enhances excitatory synaptic transmission in the rat hippocampus in vitro. Unifiram can be used in studies related to amnesia and cognitive dysfunction, including age-related memory decline, neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease, multiple sclerosis, schizophrenia, and attention deficit hyperactivity disorder.

Glycerol dioleate is a lipid capable of forming Lyotropic Liquid Crystal (LLC). When formulated with phosphatidylcholine and exposed to aqueous media, glycerol dioleate constructs an inverted hexagonal (H_II) phase structure with sustained-release properties. The in-situ forming gel prepared by optimizing glycerol dioleate with phosphatidylcholine and N-methyl-2-pyrrolidone enables stable release of Risperidone (HY-11018) for up to 60 days in vitro and in vivo. Glycerol dioleate causes minimal side effects in rabbits, making it an ideal carrier component for the development of antischizophrenia agents.Note: Lyotropic liquid crystals (Lyotropic Liquid Crystal, LLC) are ordered fluid phases self-assembled by amphipathic molecules (e.g., lipids, surfactants) in solvents (usually water) at specific concentrations.

Quinpirole (LY 171555; (-)-LY 141865) is a D2/D3 dopamine receptor agonist and a CaV1.3 calcium channel modulator. Quinpirole normalizes dendritic spine density in dopamine-depleted striatum, upregulates the protein expression of BCL2 and GluR2, downregulates the protein expression of BAX, and delays the onset of seizures. Quinpirole enhances learning and memory, inhibits neuronal apoptosis (apoptosis), and induces anxiety-like, stereotyped, and compulsive behaviors. Quinpirole disrupts prepulse inhibition in rhesus monkeys, enhances the activity of paraventricular thalamic neurons to promote recovery from Isoflurane anesthesia, and alters the composition of the gut microbiota in rats. Quinpirole can be used in research related to dyskinesia, pain, epilepsy, and neurological disorders including anxiety disorder, obsessive-compulsive disorder, and schizophrenia.

L 741742 is a highly selective and brain-penetrant D4 dopamine receptor antagonist, with K_i values of 3.5 nM, 770 nM and >1700 nM for human D4, D3 and D2 receptors, respectively. L 741742 suppresses PDGFRβ, ERK1/2, and mTOR signaling pathways, and impairs autophagic flux while disrupting lysosomal function.L 741742 induces G0/G1 cell-cycle arrest and apoptosis, promotes neuronal differentiation of normal human neural stem cells, selectively inhibits growth and clonogenic potential of glioblastoma neural stem cells and primary glioblastoma tumor cells, exerts synergistic effects with Temozolomide (TMZ) (HY-17364) against glioblastoma neural stem cells in vitro, and inhibits glioblastoma neural stem cell xenograft growth in immunocompromised mice. L 741742 can be used for the research of schizophrenia and glioblastoma.

AMPA receptor modulator-10 (Compound 9a) is an orally active AMPA receptor (AMPAR) positive allosteric modulator. AMPA receptor modulator-10 exhibits potent activity (pEC₅₀ = 5.0) on the GluA2 subtype of AMPAR, significantly enhancing glutamate-induced calcium influx and current responses. AMPA receptor modulator-10 can reverse the memory impairment induced by Scopolamine (HY-N0296) and enhance cognitive function. AMPA receptor modulator-10 can be used for the research of neurological disease, such as schizophrenia.

Iloperidone metabolite Hydroxy Iloperidone (P88; Hydroxy Iloperidone) is an active reduced metabolite of Iloperidone (HY-17410). Iloperidone metabolite Hydroxy Iloperidone can be used for the research of schizophrenia.

VU6008055 (AF98943) is a brain-penetrant, orally active and selective muscarinic acetylcholine receptor subtype 4 (mAChR4) activator with human EC₅₀ values of 73.4 nM. VU6008055 potentiates mAChR4 receptor activity in the presence of acetylcholine, and exhibits no activity at mAChR1, mAChR3, or mAChR5. VU6008055 can be used for the research of schizophrenia, parkinson’s disease, alzheimer’s disease.

KS-133 is a bicyclic peptide with VIPR2 antagonistic activity that can cross the blood-brain barrier. KS-133 selectively blocks VIPR2-mediated Gq/Ca, Gs/cAMP, cAMP/PKA/ERK and PI3K/AKT/GSK3β signaling pathways. KS-133 inhibits VIPR2 agonist-induced CREB phosphorylation in the prefrontal cortex of mice. KS-133 shifts the polarization direction of macrophages toward M1. KS-133 attenuates cancer cell proliferation and reduces the cell cycle distribution level at the S-M phase. KS-133 exerts antitumor effects in a mouse model of colorectal cancer. KS-133 reverses cognitive decline in mouse models of psychiatric disorders. KS-133 can be used for research related to schizophrenia, colorectal cancer and breast cancer.

ZJ43 is a NAAG peptidase inhibitor and glutamate carboxypeptidase II/III (GCP II/III) inhibitor with human GCP II IC₅₀ of 2.4 nM and K_i of 0.8 nM. ZJ43 blocks N-acetylaspartylglutamate hydrolysis, elevates extracellular N-acetylaspartylglutamate levels, and activates group II metabotropic glutamate receptors (mGluR). ZJ43 can be used for the research of schizophrenia, inflammatory pain, neuropathic pain, and traumatic brain injury.