ischaemic

Mildronate (Meldonium) is an inhibitor of biosynthesis of L-carnitine by gamma-butyrobetaine (GBB) hydroxylase and as a competitive inhibitor of renal carnitine reabsorption.

2-Chloroadenosine (CADO) is a metabolically stable analog of adenosine that binds to adenosine A1, A2A, and A3 receptors( Ki:300, 80, and 1,900 nM, respectively)

Limaprost (17α,20-dimethyl-δ2-PGE1) is an analog of PGE1 with structural modifications intended to give it a prolonged half-life and greater potency.It is a potent and orally active vasodilator. Limaprost increases blood flow and inhibits platelet aggregation. Limaprost (17α,20-dimethyl-δ2-PGE1) can be used for pain relief, has antianginal effects, and has potential for ischaemic symptoms treatment.

BTB06584 is an IF1-dependent, selective inhibitor of the mitochondrial F1 Fo-ATPase. BTB06584 is a novel acetohydroxyacid synthase(AHAS) inhibitor, a promising drug target against Mycobacterium tuberculosis (MTB).

Conoidin A is a cell-permeable inhibitor of the T. gondii enzyme peroxiredoxin II (TgPrxII) with nematicidal properties. It covalently binds to the peroxidatic Cys47 of TgPrxII, irreversibly inhibiting its hyperperoxidation activity with an IC50 of 23 μM. It also inhibits hyperoxidation of mammalian PrxI and PrxII (but not PrxIII). Conoidin A has antioxidant, neuroprotective effects and can be used for research on ischaemic heart disease.

Ivabradine hydrochloride (S 16257-2) is a new If inhibitor (IC50: 2.9 μM). Ivabradine Hydrochloride is the hydrochloride salt form of ivabradine, an orally bioavailable, hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel blocker, with negative chronotropic activity. Upon administration, ivabradine selectively binds to the intracellular portion of the HCN channel pore and blocks HCN channels in the pacemaker cells within the sinoatrial (SA) node. This inhibits the If (funny) pacemaker ion current, prevents the inward flow and intracellular accumulation of positively charged ions, reduces pacemaker activity and slows diastolic depolarization.

Metoprolol Tartrate is a blocker of the cardioselective β-adrenergic receptor.

Metoprolol succinate is a selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.

Atorvastatin Sodium (Lipitor) is a competitive inhibitor of HMG-CoA reductase and increases the expression of low density lipoprotein (LDL) receptors on hepatocytes. Atorvastatin Sodium treatment inhibits aquaporin 4 to reduce ischaemic brain oedema.

Trimetazidine is a non-haemodynamic antianginal agent that selectively inhibits the mitochondrial enzyme 3-ketoacyl coenzyme A thiolase (LC 3-KAT), thereby preventing β-oxidation of free fatty acids, with an IC50 value of 75 nM. Trimetazidine prevents ischaemia-reperfusion injury by altering cardiac metabolism, exhibiting antioxidant and anti-ischaemic effects.

Gavestinel (GV 150526) is a non-competitive NMDA receptor antagonist that is potent, selective and orally active.Gavestinel binds to the glycine site of the NMDA receptor with a binding affinity (pKi value) of 8.5.Gavestinel is used in acute ischaemic stroke studies.

LY231617 is an orally bioavailable, blood-brain barrier-penetrant antioxidant that mitigates systemic ischaemic neuronal injury in rats. It exerts neuroprotective effects against H₂O₂-induced toxicity by inhibiting lipid peroxidation.

VEC6 is a VEZF1–DNA interaction inhibitor that recapitulates RhoB loss in ischaemic retinopathy.

BN 50739 is an antagonist of platelet-activating factor (PAF). BN 50739 suppresses certain cardiac arrhythmias. PAF is released from ischaemic myocardium and may contribute to initiation of ischaemia-induced ventricular fibrillation (VF)

Ru360, an oxygen-bridged dinuclear ruthenium amine complex, is a selective mitochondrial calcium uptake inhibitor. Ru360 potently inhibits Ca2+ uptake into mitochondria with an IC50 of 0.184 nM. Ru360 binds to mitochondria with high affinity (Kd of 0.34 nM). Ru360 has antiarrhythmic and cardioprotective effects[1][2]. Ru360 permeates slowly into the cell, and specifically inhibits mitochondrial calcium uptake in intact cardiomyocytes and in isolated heart. 1 μm Ru360 is taken up by myocardial cells and accumulated in the cytosol in a biphasic manner[1]. During pelleting hypoxia, Ru360 (10 µM) significantly improves cell viability in wild type cardiomyocytes[3]. Ru360 (15-50 nmol/kg) treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru360 administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mitochondrial permeability transition pore (mPTP)[1]. [1]. G de J García-Rivas, et al. Ru360, a Specific Mitochondrial Calcium Uptake Inhibitor, Improves Cardiac Post-Ischaemic Functional Recovery in Rats in Vivo. Br J Pharmacol. 2006 Dec;149(7):829-37. [2]. M A Matlib, et al. Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake Into Mitochondria in Vitro and in Situ in Single Cardiac Myocytes. J Biol Chem. 1998 Apr 24;273(17):10223-31. [3]. Lukas J Motloch, et al. UCP2 Modulates Cardioprotective Effects of Ru360 in Isolated Cardiomyocytes During Ischemia. Pharmaceuticals (Basel). 2015 Aug 4;8(3):474-82.

NHE3-IN-2 is an inhibitor of NHE3 (Na+/H+ exchanger-3), applicable for treating hypertension, thrombosis, and ischaemic diseases.

Ivabradine is a potent, orally active HCN (hyperpolarization-activated cyclic nucleotide-gated) channel blocker that inhibits pacemaker current (If). ivabradine decreases heart rate in a dose-dependent manner and does not alter blood pressure. ivabradine has anticonvulsant, anti-ischaemic and anti-anginal effects.

Falipamil hydrochloride is a calcium channel antagonist potentially for the treatment of ischaemic heart disorder and sinus.

6-O-Caffeoylarbutin (Robustaside B) is a natural antioxidant capable of inducing mitochondrial membrane permeability transition. It modulates the SIRT1/PI3K/AKT/NF-κB pathway, thereby ameliorating liver injury and symptoms of ischaemic stroke in mice.

Alashinol G ((-)-Carinol) is isolated from the stem bark of Syringa pinnatifolia, a Mongolian folk medicine with anti-myocardial ischaemic effects.