cerebral artery

Annaosanchun (YC-6) is potentially for the treatment of acute ischemic stroke (AIS).

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

CaCCinh-A01 is an inhibitor of the calcium-activated chloride channel (CaCC, 10 μM) and TMEM16A (IC50: 2.1 μM).

Piclozotan (anhydrous), a 5-HT1A receptor agonist, demonstrated significant neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model, ameliorating motor complications in patients with advanced Parkinson's disease.

Pinokalant (LOE-908) is a novel non-selective cation channel inhibitor.Pinokalant significantly reduces cortical infarct volume in in vivo experiments, improves the metabolic and electrophysiological status of the ischemic penumbra region, and reduces the size of the lesion on magnetic resonance images in the acute phase after middle cerebral artery occlusion in rats.Pinokalant is a potential SARS-CoV-2 protease inhibitor for the study of stroke.

Bumetanide (PF 1593) is a potent sulfamoylanthranilic acid derivative belonging to the class of loop diuretics. In the brain, bumetanide may prevent seizures in neonates by blocking the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC1), thereby inhibiting chloride uptake thus, decreasing the internal chloride concentration in neurons and may block the excitatory effect of GABA in neonates.

Pramipexole (SND 919) is a selective dopamine receptor agonist used in the therapy of Parkinson disease. Pramipexole therapy is associated with a low rate of transient serum enzyme elevations during treatment but has not been implicated in cases of clinically apparent acute liver injury.

2,2,2-Trichloroethanol, the active form of the sedative hypnotic drug chloral hydrate, is an agonist for the nonclassical K2P channels TREK-1 (KCNK2) and TRAAK (KCNK4). It activates a nonclassical potassium channel in cerebrovascular smooth muscle and dilates the middle cerebral artery [1]. [1]. Nikhil K Parelkar, et al. 2,2,2-trichloroethanol Activates a Nonclassical Potassium Channel in Cerebrovascular Smooth Muscle and Dilates the Middle Cerebral Artery. J Pharmacol Exp Ther. 2010 Mar;332(3):803-10.

Pramipexole dihydrochloride hydrate (Mirapex) is the hydrochloride salt of pramipexole, a benzothiazole derivative. As a nonergot dopamine agonist, pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra of the brain.

The quinuclidine PHA 568487 free base is an agonist of the alpha 7 nicotinic acetylcholine receptor that was designed to mitigate the bioactivation associated with the core scaffold and subsequently remove associated liabilities with in vivo tolerability.

SMND-309, a metabolite of salvianolic acid B, exhibits neuroprotective effects in cultured neurons and in rats subjected to permanent middle cerebral artery occlusion.

Nicotinoyl cyclandelate can effectively reduce blood pressure in the femoral artery and perfusion pressure in cerebral blood vessels.

Neuroprotective agent 6 (Compound Y12) functions as an antioxidant and displays prominent neuroprotective effects in both oxygen-glucose deprivation/reperfusion (OGD/R) induced cell models and transient middle cerebral artery occlusion (tMCAO) induced animal models. Additionally, this compound shows significant metal chelating activity towards Cu2+.

TREK inhibitor-3 (Cpd8l) is a selective inhibitor of TREK-1 that can cross the blood-brain barrier, with an IC50 of 0.81 μM. It offers neuroprotective effects by significantly reducing cortical neuron death induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and alleviating brain injury in middle cerebral artery occlusion/reperfusion (MCAO/R) model mice. TREK inhibitor-3 is utilized in ischemic stroke research.

P2Y1 antagonist 3 (compound 36b) is a P2Y1 antagonist capable of penetrating the blood-brain barrier (BBB), with an IC50 value of 0.50 μM. In a rat middle cerebral artery occlusion (MCAO) model, it demonstrates protective properties and exhibits neuroprotective effects against oxidative stress by upregulating Nrf2 protein levels.

RIPK1-IN-33 is an orally active RIPK1 inhibitor with excellent blood-brain barrier permeability, exhibiting an IC50 of 0.115 μM. It demonstrates significant anti-ferroptosis activity, radical scavenging capability (IC50= 123.3 μM), and anti-lipid peroxidation effects (IC50= 9.72 μM). In transient middle cerebral artery occlusion (tMCAO) models, it significantly reduces cerebral infarct volume and improves neurological scores. RIPK1-IN-33 is suitable for ischemic stroke research.

Nrf2 activator-21 is a compound that serves as an Nrf2 activator with both antioxidant and neuroprotective properties. It binds to the Keap1Kelch domain, disrupting the Keap1-Nrf2 interaction and activating antioxidant defense mechanisms. Nrf2 activator-21 decreases apoptosis of hippocampal neurons and reduces caspase-3 activity. It targets cerebral ischemia/reperfusion injury (CIRI) by activating the Nrf2 pathway. The compound improves neurological function, alleviates anxiety-like behavior induced by bilateral carotid artery occlusion (2VO) in rats, and enhances memory. Nrf2 activator-21 is applicable in studies of cerebral ischemia/reperfusion injury.

AS604872 is a selective antagonist of the FP receptor.. AS604872 significantly accelerated degeneration of the media in both cerebral artery and aorta as evidenced by thinning of the media and disruption of the elastic lamina and promoted IA and aortic di

Daurinoline is a non-competitive antagonist, it exerts marked relaxation effect on basilar artery of rabbits through non-competitive antagonism, it would have a protective function on microcirculation of cerebral pia mater, which may be beneficial to relieve cerebral ischemic injury. Daurinoline could significantly reverse noradrenaline induced constriction of pial arterioles and venules, and increase the number of blood vessels which were decreased by noradrenaline.

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .1,217R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BKCa) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.2It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC50= ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.3,4 1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties that protects mice from ischemic stroke by counteracting intracerebral thrombosis in the tMCAO model.L-Palmitoylcarnitine chloride (Palmitoyl-L-carnitine chloride) is a fatty acid metabolite with antithrombotic properties. Palmitoylcarnitine chloride inhibits the Na/K pump in the heart and inhibits FeCl 3-induced arterial thrombosis Attenuates intracerebral thrombosis and inflammation in a mouse model of transient middle cerebral artery occlusion (tMCAO).

LFHP-1c is a novel PGAM5 inhibitor that shows neuroprotective activity in an ischemic stroke model, preventing BBB destruction after transient middle cerebral artery occlusion (tMCAO) in rats.LFHP-1c can be used to study cerebral ischemic stroke.

PKCd (8-17) is a bioactive peptide originating from the V1 domain of protein kinase C (PKC)d. It impedes phorbol 12-myristate 13-acetate (PMA)-stimulated PKCd translocation and activation, which mitigates ischemic injury in cardiac and cerebral cells, promotes fibroblast proliferation, and suppresses graft coronary artery disease in [mouse models].