Detomidine produce dose-dependent sedative and analgesic effects, is a nonnarcotic, synthetic α2-adrenergic agonistTarget: α2-adrenergic agonistDetomidine is an imidazole derivative and α2-adrenergic agonist, used as a large animal sedative, primarily used in horses. It is usually available as the salt detomidine hydrochloride. It is a prescription medication available to veterinarians sold under the trade name Dormosedan. Currently, detomidine is only licenced for use in horses.Detomidine is a sedative with analgesic properties. α2-adrenergic agonists produce dose-dependent sedative and analgesic effects, mediatated by activation of α2 catecholamine receptors, thus inducing a negative feedback response, reducing production of excitatory neurotransmitters. Due to inhibition of the sympathetic nervous system, detomidine also has cardiac and respiratory effects and an antidiuretic action.
AChE/BuChE-IN-2 (Compound 5f) is an orally active AChE and BuChE inhibitor with IC50 values of 0.72 μM and 0.16 μM, respectively. AChE/BuChE-IN-2 shows a non-competitive inhibition with AChE and shows potent self-induced β-amyloid (Aβ) aggregation inhibition with an IC50 of 62.52 μM. AChE/BuChE-IN-2 can cross the BBB[1].
Valepotriate, isolated from Valeriana jatamansi Jones, has anti-epileptic and anti-cancer activities[1][2].
BIM 23056, a linear octapeptide, is a potent sst3 and sst5 somatostatin receptor antagonist with Ki values of 10.8, 5.7, respectively[1].
Proglumide sodium is a nonpeptide and orally active cholecystokinin (CCK)-A/B receptors antagonist. Proglumide sodium selective blocks CCK’s effects in the central nervous system (CNS). Proglumide sodium has ability to inhibit gastric secretion and to protect the gastroduodenal mucosa. Proglumide sodium also has antiepileptic and antioxidant activities[1][2][3][4][5].
Glycopyrrolate(Glycopyrronium Br) is a muscarinic competitive antagonist used as an antispasmodic.IC50 Value:Target: mAChR (Muscarinic acetylcholine receptor M1)in vitro: Glycopyrrolate showed no selectivity in its binding to the M1-M3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [3H]-NMS binding at 30 nM) compared to ipratropium bromide [1].in vivo: Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week six and 4 days of week seven when the daily dose was reduced to two tablets for 3 days. glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken [2]. Glycopyrrolate has a slow and erratic absorption from the gastrointestinal system, but even low plasma levels are associated with a distinct and long-lasting antisialogic effect [3]. Oral glycopyrrolate is emerging as a potential second-line treatment option, but experience with safety, efficacy, and dosing is especially limited in children [4]. phase III study, 52.3% of glycopyrrolate oral solution recipients (aged 3-18 years; n = 137) had an mTDS response (primary endpoint); the response rate was consistently above 50% at all 4-weekly timepoints, aside from the first assessment at week 4 (40.3%). In general, glycopyrrolate oral solution was well tolerated in clinical trials. The majority of adverse events were within expectations as characteristic anticholinergic outcomes [5].Toxicity: Side effects include dry mouth, difficult urinating, heachaches, diarrhea and constipation. The medication also induces drowsiness or blurred vision. LD50=709 mg/kg (rat, oral).
BACE1-IN-6 is a BACE1 inhibitor with an IC50 value of 1.5 nM.
NPEC- caged-(S)-AMPA, a caged neurotransmitter analog, is a NPEC photoprotecting group caged the (S)-AMPA (HY-100815A) to make caged ligands specific for glutamate receptor sub-types. NPEC- caged-(S)-AMPA selectively activates AMPA receptor[1].
Curculigoside C is a phenolic glucoside with potent antioxidative and neuroprotective activities. Curculigoside C shows IC50 values of 0.25 mM and 0.88 mM for hydroxyl radicals and superoxide anion radicals, respectively[1].
[D-Ala2]-Met-Enkephalin, an opioid peptide, is a potent opioid agonist. [D-Ala2]-Met-Enkephalin inhibits ACh-induced and suckling-induced oxytocin (OT) release[1][2].
Pomaglumetad methionil (LY2140023 hydrate) is an oral methionine prodrug of the potent specific mGlu2/3 receptor agonist LY404039 (HY-50906). Pomaglumetad methionil is well-tolerated and has a distinct safety profile, and can be used to treat schizophrenia[1][2].
JMV 2959 is a growth hormone secretagogue receptor type 1a (GHS-R1a) antagonist with an IC50 of 32 nM.
Lazabemide hydrochloride (Ro 19-6327 hydrochloride) is a selective, reversible inhibitor of monoamine oxidase B (MAO-B) (IC50=0.03 μM) but less active for MAO-A (IC50>100 μM). Lazabemide inhibits monoamine uptake at high concentrations, the IC50 values are 86 μM, 123 μM and >500 μM for noradrenalin, serotonin and dopamine uptake, respectively. Lazabemide can be used for the research of parkinson and alzheimer′s disease[1].
Tau-aggregation and neuroinflammation-IN-1 is a potent tau-aggregation and neuroinflammation inhibitor. Tau-aggregation and neuroinflammation-IN-1 exhibits remarkable inhibitory activities against AcPHF6 and full-length tau aggregation. Tau-aggregation and neuroinflammation-IN-1 has a low cytotoxicity and reduced NO release in LPS-stimulated BV2 cells. Tau-aggregation and neuroinflammation-IN-1 can reverse okadaic acid-induced memory impairment in rats[1].
Tolperisone is a centrally acting muscle relaxant, is indicated for use in the treatment of pathologically increased tone of the cross-striated muscle caused by neurological diseases (damage of the pyramidal tract, multiple sclerosis, myelopathy, encephalomyelitis) and of spastic paralysis and other encephalopathies manifested with muscular dystonia.
TREM2 agonist-1 (I-246) is a triggering receptor expressed on myeloid cells 2 (TREM2) agonist (EC50 between 3.0 μM and 100 μM)[1].
L-Glutamic acid-5-13C is the 13C-labeled L-Glutamic acid. L-Glutamic acid acts as an excitatory transmitter and an agonist at all subtypes of glutamate receptors (metabotropic, kainate, NMDA, and AMPA). L-Glutamic acid shows a direct activating effect on the release of DA from dopaminergic terminals.
SCH-23390-d3 (R-(+)-SCH-23390-d3) hydrochloride is the deuterium labeled SCH-23390 hydrochloride. SCH-23390 hydrochloride (R-(+)-SCH-23390 hydrochloride) is a potent and selective dopamine D1-like receptor antagonist with Kis of 0.2 nM and 0.3 nM for the D1 and D5 receptor, respectively. SCH-23390 hydrochloride is a potent and high efficacy human 5-HT2C receptor agonist with a Ki of 9.3 nM. SCH-23390 hydrochloride also binds with high affinity to the 5-HT2 and 5-HT1C receptors. SCH-23390 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channels with an IC50 of 268 nM[1][2][3].
Arecoline Hydrobromide is a muscarinic acetylcholine receptor agonist. Target: mAChRArecoline is an alkaloid found in the areca nut. Arecoline. a drug obtained from the Areca Catechu L., induced a dose-dependent antinociception (0.3-1 mg kg(-1) i.p.) which was prevented by the muscarinic antagonists pirenzepine (0.1 microg per mouse i.c.v.) and S-(-)-ET-126 (0.01 microg per mouse i.c.v.) [1]. Arecoline exerts its excitatory actions by binding to M2-muscarinic receptors on the cell membrane of neurons of the locus coeruleus [2]. Arecoline (1 nM - 1 microM) produced a concentration-dependent contraction in both the longitudinal and the circular smooth muscle of rabbit colon. Atropine (10 microM) abolished the arecoline (80 nM)--induced contraction. M3 receptor antagonist, 4 - DAMP (0.4 microM), abolished the arecoline (80 nM)--related response, whereas M2 receptor antagonist, gallamine (0.4 microM), did not affect the effect of arecoline. These results suggest that arecoline excites the colonic motility via M3 receptor in rabbits [3].
Fentonium bromide is an anti-ulcerogenic, anticholinergic and antispasmodic agent. Fentonium bromide can be used in the research of neurological conditions[1][2][3].
Supercinnamaldehyde is a potent transient receptor potential ankyrin 1 (TRPA1) activator with an EC50 value of 0.8 μM. Supercinnamaldehyde activates TRPA1 ion channels through covalent modification of cysteines[1].
CGP36216 (Compound 9) is a GABAB receptor antagonist. CGP36216 binds to GABAB receptor with a Ki value of 0.3 μM. CGP36216 can be used for research of anxiety and trauma-related disorders[1][2].
α5IA (L-822179) is a selective α5 GABAA receptor inverse agonist with neuroprotective potential[1].
Yhhu-3792 is a novel small molecule that enhances the self-renewal capability of neural stem cells (NSCs) in vitro and in vivo via activating the Notch signaling pathway; activates Notch signaling pathway and promotes the expression of Notch target genes, Hes3 and Hes5; expands the NSCs pool and promotes endogenous neurogenesis in the hippocampal dentate gyrus (DG) after chronic administration in mice.
CGP 20712 dihydrochloride is an antagonist of β 3-adrenoceptor. CGP 20712 dihydrochloride inhibits isoproterenol with the IC50 of 79 μM[1].
PACAP (6-38), human, ovine, rat is a potent PACAP receptor antagonist with IC50s of 30, 600, and 40 nM for PACAP type I receptor, PACAP type II receptor VIP1, and PACAP type II receptor VIP2, respectively.
SDZ NKT 343 is a selective, orally active NK1 receptor antagonist with an IC50 of 0.62 nM against human NK1 receptor. SDZ NKT 343 has good analgesic activity[1][2].
OXA(17-33) is a potent and selective orexin-1 receptor (OX1) agonist. OXA(17-33) shows a ∼23-fold selectivity for the OX1 (EC50=8.29 nM) over OX2 (187 nM)[1].
Rizatriptan Benzoate(Maxalt) is a 5-HT1 agonist triptan drug for the treatment of migraine headaches.Target: 5-HT1 agonist Rizatriptan Benzoate(Maxalt) is a 5-HT1 agonist triptan drug for the treatment of migraine headaches. It is believed to work by narrowing the blood vessels around the brain. Rizatriptan also reduces the substances in the body, which can also reduce headache pain, nausea, sensitivity to light and sound and other migraine symptoms.Rizatriptan was rapidly absorbed with a median tmax of 1.3 h (range 1-3 h) vs a tmax for sumatriptan of 2.5 h (range 1-4 h, P < 0.001). Administration of either rizatriptan or sumatriptan produced maximal mean elevations of 5-10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following rizatriptan, consistent with more rapid absorption. Both rizatriptan and sumatriptan provoked mild increases in serum growth hormone without any effect on serum prolactin concentrations. The most commonly reported symptom following rizatriptan was drowsiness.
JNJ-1661010 (Takeda-25) a potent and selective fatty acid amide hydrolase (FAAH) inhibitor with IC50s of 34 and 33 nM for rat FAAH and human FAAH, respectively. JNJ-1661010 can cross the blood-brain barrier and used as broad-spectrum analgesics[1][2].