Disease relevance of NICORANDIL

• We report a series of five patients with non-specific anal ulceration, all of whom received nicorandil for symptomatic control of ischaemic heart disease [1].
• Association of major aphthous ulcers and nicorandil [2].
• Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia [3].
• Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water [3].
• The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs [3].

Psychiatry related information on NICORANDIL

• After recovery from surgery, body temperature, heart rate and locomotor activity were recorded during control, saline or nicorandil (10 mg x kg(-1) administered orally) treatment and for 5 days after treatment [4].
• Influences of psychological stress produced by intraspecies emotional communication on nicorandil plasma levels in rats [5].

High impact information on NICORANDIL

• Exposure of arteries in vitro to nicorandil (10(-9)-10(-7)M) (a drug which acts by increasing gk) hyperpolarized the muscle cells and increased internal diameter [6].
• Infusion of nicorandil (3-5 micrograms/kg per min) to intact, anesthetized animals reversed, by 50%, the reduction in basilar artery diameter after experimental SAH [6].
• In control patients, the effect of epinephrine and that of additional nicorandil and propranolol on repolarization parameters were much less than in the LQT1 patients [7].
• CONCLUSIONS: Our results suggest that nicorandil, a K+ channel opener, improves repolarization abnormalities in the LQT1 form of congenital long-QT syndrome with KvLQT1 defect [7].
• Cardioplegia consisted of Krebs-Henseleit solution either alone (control) or with nicorandil (100 micromol/L, 300 micromol/L, or 1 mmol/L), 20 mmol/L KCl, or nicorandil (100 micromol/L) plus glibenclamide (10 micromol/L), a potassium channel blocker [8].

Chemical compound and disease context of NICORANDIL

• In an attempt to find conditions which prevent the deleterious effects of ischemia, representatives of three different classes of K+ channel openers, (-)-cromakalim, nicorandil, and pinacidil, were administered both before ischemia and during the reperfusion period [9].
• Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate [3].
• This randomized, double-blind, parallel study compared the anti-anginal effects of nicorandil and atenolol in 37 patients with exercise-induced angina pectoris [10].
• Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model [11].
• Hypoxic preconditioning (HP) and pharmacological preconditioning, using diazoxide (30 microM) or nicorandil (100 microM), also increased the time taken to induce the mPT by 2.0-, 2.1-, and 1.5-fold, respectively (P < 0.001), and rigor contracture by 1.9-, 1.7-, and 1.5-fold, respectively, compared with control (P < 0.001) [12].

Biological context of NICORANDIL

• There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy [13].
• One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration [14].
• Nicorandil (100 microM) suppressed all of these markers of apoptosis [15].
• RESULTS: The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group [16].
• CONCLUSIONS: Our findings identify nicorandil as an inhibitor of apoptosis induced by oxidative stress in cardiac myocytes, and confirm the critical role of mitoK(ATP) channels in inhibiting apoptosis [15].

Anatomical context of NICORANDIL

• In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil [17].
• Nicorandil activated Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its specificity for cardiac and smooth muscle K(ATP) channels [18].
• The aim of this study was to investigate the domains of the K(ATP) channel involved in nicorandil activity and to determine whether nicorandil interacts with hypoglycemic sulfonylureas that target K(ATP) channels in pancreatic beta-cells [18].
• Antiapoptotic effect of nicorandil mediated by mitochondrial atp-sensitive potassium channels in cultured cardiac myocytes [15].
• Furthermore, mitochondria from ischemic hearts had significantly (p <.05) less ability to resist swelling on Ca2+ loading, which was improved by both IP and Nic [19].

Associations of NICORANDIL with other chemical compounds

• OBJECTIVES: This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans [20].
• Similarly, the change in low frequency oscillations of systolic blood pressure was -79 +/- 144 mm Hg-Hz-1/2 during nitroglycerin administration and 60 +/- 139 mm Hg-Hz-1/2 during nicorandil administration (p = 0.04) [21].
• The effect of three potassium channel openers, nicorandil, aprikalim, and bimakalim, on experimental myocardial ischaemia/reperfusion injury was examined in barbital-anaesthetized dogs [22].
• To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation [23].
• The non-selective KATP channel openers nicorandil and cromakalim did not improve viability [24].

Gene context of NICORANDIL

• Nicorandil activated SUR2x(D834N, E1471Q)/Kir6.2 channels more strongly in the presence of Na-ATP than K-ATP alone, whereas the reverse was true for wild-type SUR2x/Kir6.2 channels [25].
• The nucleotide-binding domains of sulfonylurea receptor 2A and 2B play different functional roles in nicorandil-induced activation of ATP-sensitive K+ channels [26].
• High concentrations of intravenous nicorandil, a potassium channel opener, have been shown to be capable of decreasing QT and TDR, and preventing TdP in LQT1 and LQT2 but not in LQT3 [27].
• CONCLUSIONS: It is well known that PAI activity determines the whole fibrinolytic capacity and oral administration of nicorandil decreased PAI activity in patients with coronary artery disease [28].
• Thus, the SUR2A/Kir6.2 channels' response to nicorandil critically depends on ATP-NBD1 interaction and is facilitated by interactions of ATP or ADP with NBD2 [26].

Analytical, diagnostic and therapeutic context of NICORANDIL

• Nicorandil, but not ISDN, improved %SS during reperfusion [3].
• CONCLUSIONS: Nicorandil (100 micromol/L and 1 mmol/L) significantly improved functional recovery compared with control and was as effective as KCl cardioplegia [8].
• Moreover, nicorandil has been approved for human use and has not been shown to exhibit significant toxicity in clinical trials [8].
• METHODS: We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41) [16].
• CONCLUSIONS: Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI [16].

References