Conophylline is a vinca alkaloid extracted from leaves of a tropical plant Ervatamia microphylla. Conophylline is a differentiation inducer of for pancreatic cells. Conophylline suppresses HSC and induces apoptosis[1][2].
S1RA(E-52862) is a potent and selective sigma-1 receptor(σ1R, Ki=17 nM) antagonist, showed good selectivity against σ2R (Ki > 1000 nM).IC50 value: 17 nM (Ki) [1]Target: σ1Rin vitro: S1RA behaved as a highly selective σ1 receptor antagonist. It showed high affinity for human (Ki= 17 nM) and guinea pig (Ki= 23.5 nM) σ1 receptors but no significant affinity for the σ2 receptors (Ki > 1000 nM for guinea pig and rat σ2 receptors). Moderate affinity (Ki= 328 nM) and antagonistic activity, with very low potency (IC50= 4700 nM) was found at the human 5-HT2B receptor. S1RA showed no significant affinity (Ki > 1 μM or % inhibition at 1 μM < 50%) for other additional 170 targets (receptors, transporters, ion channels and enzymes) [2].in vivo: Control (non-operated) and nerve-injured mice received a single or repeated (twice daily for 12 days) i.p. administration of S1RA at 25 mg·kg?1, the same dose used for the assessment of behavioural hypersensitivity in the chronic treatment study. Acute treatment was given on day 12 post-surgery and repeated treatment with S1RA started the day of surgery, as in the behavioural studies [2]. Intrathecal pre-treatment with idazoxan prevented the systemic S1RA antinociceptive effect, suggesting that the S1RA antinociception depends on the activation of spinal α2 -adrenoceptors which, in turn, could induce an inhibition of formalin-evoked glutamate release. When administered locally, intrathecal S1RA inhibited only the flinching behavior, whereas intracerebroventricularly or intraplantarly injected also attenuated the lifting/licking behavior [3].
Homatropine Methylbromide is muscarinic AChR antagonist, inhibits endothelial and smooth muscle muscarinic receptors of WKY-E and SHR-E with IC50 of 162.5 nM and 170.3 nM, respectively.target： mAChRIC 50: WKY-E(162.5 nM), SHR-E(170.4nM )In vitro: Homatropine (20 μM) alone produces a dose ratio of 259 in atrium from guinea-pigs. Homatropine (20 μM) produces a dose ratio of only 95.0 when combined with hexamethonium in atrium from guinea-pigs.In vivo: : Pre-treatment with homatropine (20 mg/kg) was comparable with atropine (10 mg/kg) in preventing lethality in this rat model of acute OC poisoning. All rats pre-treated with normal saline, atropine 5 mg/kg, and homatropine 10 mg/kg died. Survival in the homatropine (20 mg/kg) and atropine (10 mg/kg) groups was 30% and 40% respectively.
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
NK1 receptor antagonist 2 is a NK1 receptor antagonist. NK1 receptor antagonist 2 can be used for the research of tinnitus and hearing loss[1].
Venlafaxine hydrochloride is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.Target: SNRIVenlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder (MDD), as a treatment for generalized anxiety disorder, and comorbid indications in certain anxiety disorders with depression. In 2007, venlafaxine was the sixth most commonly prescribed antidepressant on the U.S. retail market, with 17.2 million prescriptions.Venlafaxine is a bicyclic antidepressant, and usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin and norepinephrine. Additionally, in high doses it weakly inhibits the reuptake of dopamine, with recent evidence showing that the norepinephrine transporter also transports some dopamine as well, since dopamine is inactivated by norepinephrine reuptake in the frontal cortex. The frontal cortex largely lacks dopamine transporters; therefore, venlafaxine can increase dopamine neurotransmission in this part of the brain. Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter (to measure pain), both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following intraperitoneal injection. These findings suggest venlafaxine's seemingly superior efficacy in severe depression as narcotics become increasingly used as a measure of last resort for refractory cases.
AZD 2066 is a selective, orally active and brain-penetrant mGluR5 antagonist, with analgesia activity[1].
Leteprinim potassium (AIT-082) is a hypoxanthine derivative neurotrophic agent. Leteprinim potassium can induce brain-derived neurotrophic factor (BDNF) mRNA production following spinal cord lesions, and nerve growth factor (NGF) mRNA production in basal forebrain. Leteprinim potassium reduces glutamate toxicity in cultured hippocampal neurons. Leteprinim potassium increases heme-oxygenase 1 and 2 mRNA levels that play role in cellular defense against reactive oxygen species. Leteprinim potassium has neuroprotective activity[1].
Linarin (Buddleoside), isolated from the flower extract of Mentha arvensis, shows selective dose dependent inhibitory effect on acetylcholinesterase (AChE)[1].
VUF 5681 dihydrobromide is a neutral antagonist of histamine H3 receptor. VUF 5681 dihydrobromide also has partial agonist function of H3 receptor. VUF 5681 dihydrobromide blocks the effects of Thioperamide (HY-12206). VUF 5681 dihydrobromide is used in central nervous system disease research[1][2].
Carbonic anhydrase is ubiquitous zinc-containing metalloenzyme present in prokaryotes and eukaryotes. Carbonic anhydrase can catalyze reversible conversion of carbon dioxide to bicarbonate and protons. Carbonic anhydrase can be used for the research of cancer, glaucoma, obesity and epilepsy[1][2].
NTR 368 is a peptide derived from p75 neurotrophin receptor (p75NTR) corresponding to residues 368-381 of the human receptor. NTR 368 has helix forming propensity in the presence of micellar lipid. NTR 368 is a potent inducer of neural apoptosis[1].
(±)-LY367385 is the racemate of LY367385. LY367385 is a highly potent and selective mGluR1a antagonist. LY367385 has an IC50 of 8.8 μM for inhibits of quisqualate-induced phosphoinositide (PI) hydrolysis, compared with > 100 μM for mGlu5a[1][2].
Bemesetron (MDL 72222) is a selective 5-HT3 receptor antagonist with an IC50 of 0.33 nM[1]. Neuroprotective effects[2].
Thio-ITP (6-Thioinosine 5′-triphosphate) is a RNA polymerase activities competitive inhibitor[1].
Fabomotizole Hcl (CM346 Hcl) is an anxiolytic drug; produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions.IC50 value:Target: anxiolytic agent Afobazole's mechanism of action remains poorly defined however, with GABAergic, NGF and BDNF release promoting, MT1 receptor antagonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Afobazole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors. Afobazole has found little clinical use outside of Russia and has not been evaluated by the FDA.
Filapixant is a purinoreceptor antagonist extracted from patent WO2016091776A1, example 348. Filapixant is the active reference substance of Eliapixant[1].
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].
Atracurium Besylate is a neuromuscular blocking agent with ED95 of 0.2 mg/kg. Target: nAChRAtracurium besylate is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. Atracurium is classified as an intermediate-duration non-depolarizing neuromuscular-blocking agent [1]. A 14C radiolabeled metabolism study in cats confirmed the lack of hepatic or renal involvement in the metabolism of atracurium: radioactivity eliminated in bile and urine was predominantly from metabolites rather than the unchanged parent drug [2].
MCOPPB is an orally active and selective agonist of Nociceptin/Orphanin FQ–Receptor. MCOPPB inhibits signaling through the NOP receptor in the mouse brain. MCOPPB is used in anxiety disorders research[1].
H-Ser-Tyr-OH is a dipeptide consisting of glutamic acid, glycine and histidine. H-Ser-Tyr-OH can form a copper(II) complex with copper ions to form a strong free radical scavenging activity. H-Ser-Tyr-OH also increases the intracellular uptake of the delta opioid receptor ligand deltorphin[1].
ZK 93423 is a potent benzodiazepine GABAA receptor agonist with a certain cooling effect on rodents[1].
Loperamide D6 hydrochloride (R-18553 D6 hydrochloride) is a deuterium labeled Loperamide hydrochloride. Loperamide hydrochloride is an opioid receptor agonist for the treatment of diarrhea[1].
Bavisant Hcl hydrate(JNJ-31001074) is a highly selective, orally active antagonist of the human H3 receptor with a novel mechanism of action, involving wakefulness and cognition, with potential as a treatment for ADHD. IC50 Value: Target: H3 receptorin vitro: Bavisant completed a phase II ADHD trial, but no results have been reported [1].in vivo: Mean change from baseline in the total ADHD-RS-IV score at day 42 (primary efficacy endpoint) was -8.8 in the placebo group versus -9.3, -11.2 and -12.2 in the bavisant 1?mg/day, 3?mg/day and 10?mg/day groups, respectively; the change in the 10?mg/day group was not statistically superior to placebo (p=0.161), and hence statistical comparisons of the 1?mg/day and 3?mg/day groups with placebo based on a step-down closed testing procedure were not performed [2].Clinical trial: A Study to Characterize the Pharmacokinetics and Effect of Food on JNJ-31001074 in Healthy Volunteers. Phase 2
Picrotin is an inhibitor of glycine receptors (GlyRs) which blocks α2 GlyR, α1 GlyR and α3 GlyR[1][2].
A 438079 is a potent, and selective P2X7 receptor antagonist with pIC50 of 6.9.
Sulfo-ara-F-NMN (CZ-48) is a mimetic of nicotinamide mononucleotide (NMN). Sulfo-ara-F-NMN acts selectively, activating SARM1 but inhibiting CD38 (IC50 around 10 μM). Sulfo-ara-F-NMN induces intracellular cyclic ADP-ribose (cADPR) production[1].
D-KLVFFA is the inhibitor of Amyloid-β assembly, with the IC50 of 2.6 μM, that can be used in Alzheimer's disease study[1].
BU09059 is a potent, selective, short-acting kappa-opioid receptor antagonist with Ki of 1.72 nM, displays 15- and 616-fold selectivity over μ- and δ-receptors respectively; BU09059 is a potent and selective κ-antagonist with pA2 of 8.62, significantly blocks U50,488-induced antinociception in vivo (3 and 10 mg/kg), demonstrates a shorter duration of κ-antagonist action in vivo.