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PubMed1999

Early increases in renal kallikrein secretion on administration of potassium or ATP-sensitive potassium channel blockers in rats.

1 This study aimed to examine whether administration of potassium or ATP-sensitive potassium channel (KATP channel) blockers caused early increases in renal kallikrein (KK) secretion. To clarify this mechanism, the effect on renal KK secretion of a KATP channel blocker was compared with the effect resulting from use of an osmotic diuretic or volume load. Furthermore, the effect on potassium-induced increases in renal KK secretion by an additional treatment using a KATP channel blocker was examined. Lastly, the effect of a KATP channel blocker on renal KK secretion was also examined in superfused slices of kidney cortex. 2 Intravenous infusion of potassium augmented renal KK secretion within 30 min while urine volume increased gradually in both the potassium loading and control groups. 3 Administration of the KATP channel blocker, 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (PNU-37883A) or glibenclamide, caused a dose-dependent increase in renal KK secretion. 4 The concentration of KK in urine was higher in the PNU-37883A group as compared to the osmotic-diuretic or volume-load group. 5 PNU-37883A had no additive effect on the potassium-induced increase in renal KK secretion. 6 Renal KK secretion increased in slices of kidney cortex incubated with PNU-37883A within 10 min of superfusion. 7 In conclusion, administration of both potassium and KATP channel blockers induced early increases in renal KK secretion in the absence of the washout phenomenon. Potassium loading may have increased renal KK secretion through the same mechanism as the KATP channel blocker.

Adamantane↗
PubMed2004

In vivo electrophysiological effects of a selective slow delayed-rectifier potassium channel blocker in anesthetized dogs: potential insights into class III actions.

OBJECTIVES: This study evaluated the in vivo electrophysiological effects of a highly selective slow delayed-rectifier K+-current blocker, HMR 1556, to gain insights into the consequences of selectively inhibiting the slow delayed-rectifier current in vivo. METHODS: Atrial and ventricular effective refractory periods, sinus node recovery time, Wenckebach cycle-length, atrial fibrillation duration and electrocardiographic intervals were measured before and after intravenous HMR 1556. RESULTS: HMR 1556 increased atrial and ventricular refractory periods (e.g. by 6 +/- 4% and 27 +/- 6% at cycle lengths of 360 and 400 ms, respectively), QT intervals and sinus-node recovery times. Beta-adrenoceptor blockade with nadolol abolished all effects except those on ventricular refractoriness and changed positive use-dependent effects on refractoriness to reverse use-dependent ones. In the presence of dofetilide to block rapid delayed-rectifier current, HMR 1556 effects were potentiated (e.g. atrial and ventricular refractory periods increased by 26 +/- 3% and 34 +/- 3% at cycle lengths of 360 and 400 ms, respectively). HMR 1556 reduced vagal atrial fibrillation duration from 1077 +/- 81 to 471 +/- 38 s, an effect abolished by nadolol and greatly potentiated by dofetilide (duration 77 +/- 30 s). HMR 1556 increased Wenckebach cycle length only in the presence of dofetilide. CONCLUSIONS: Slowed delayed-rectifier current inhibition affects atrial repolarization, sinus node function and atrial fibrillation in vivo, but only in the presence of intact beta-adrenergic tone, and delays ventricular repolarization even when beta-adrenoceptors are blocked. The slow delayed-rectifier current is particularly important when rapid delayed-rectifier current is suppressed, illustrating the importance of repolarization reserve.

Adrenergic beta-Antagonists↗
PubMed1993

[Changes in endocochlear potential induced by potassium-channel blockers].

The effect of various potassium-channel blockers, 4-aminopyridine (4-AP), tetraethylammonium (TEA) and quinine, on the endocochlear potential (EP) was studied in perfused guinea pig inner ears. The fast K(+)-channel blocker, 4-AP, did not alter EP but changed its response model to intense noise exposure. While TEA and quinine significantly reduced the amplitude of negative component of EP (N-EP), comparing with a relatively smaller increase in general EP (G-EP). The results indicated the existence of different K(+)-channels with different physiological functions.

4-Aminopyridine↗
PubMed1989

Anti-ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker glyburide.

The direct cardioprotective efficacy of the potassium channel activators pinacidil and cromakalim was determined in isolated globally ischemic rat hearts. Isolated buffer-perfused rat hearts were subjected to 25 min of ischemia followed by 30 min of reperfusion. These hearts were pretreated with 1 to 100 microM pinacidil, 1 to 7 microM cromakalim or vehicle. Pinacidil resulted in significant improvements in reperfusion function and cardiac compliance, though it did not significantly reduce lactate dehydrogenase release at any concentration. The protective effects of pinacidil were greatest at a 10 microns concentration and were slightly diminished at higher concentrations (30 and 100 microns). Although not affecting the severity of ischemia alone, 10 microM glyburide (potassium channel blocker) completely reversed the protective effects of pinacidil on reperfusion function and compliance. Cromakalim (7 microM) resulted in a greater than 50% improvement in reperfusion function and compliance and unlike pinacidil significantly reduced lactate dehydrogenase release by approximately 50%. At 1 microM, glyburide alone did not significantly affect the severity of ischemia but reversed the protective effects of cromakalim. Not only did glyburide reverse the protective effects of cromakalim, it resulted in a worsening of ischemia compared to vehicle, an effect not seen with glyburide alone. Thus, both pinacidil and cromakalim appear to have direct cardioprotective efficacy, though some differences between them may be possible. The mechanism of their protective effects appears to be via potassium channel opening as the potassium channel blocker glyburide reverses the protective effect of these compounds. Intracellular electrophysiological studies showed that ischemia-induced depolarization was reversed with cromakalim, which increased the resting potential nearly back to preischemic levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Effects of potassium channel blockers on resting tone in isolated coronary arteries.

The effects of several potassium channel blockers on resting vasomotor tone were studied in porcine isolated coronary arteries. Coronary artery rings were suspended in organ baths for isometric tension recording. The nonselective potassium channel blockers tetraethylammonium (TEA 10(-5)-3 x 10(-2) M) and 4-aminopyridine (4-AP 10(-5)-10(-2) M) caused concentration-dependent contractions that were similar in rings with and without endothelium. The concentration-response curves to TEA and 4-AP were unaffected by treatment with phentolamine (3 x 10(-6) M),propranolol (10(-6) M), or atropine (10(-6) M). Diltiazem (10(-6) M) almost abolished the contractions evoked by TEA and 4-AP. Charybdotoxin (10(-9)-10(-7) M) and apamin (10(-8)-10(-6) M), selective blockers of large and small calcium-activated potassium channels, respectively, and glyburide (10(-8)-10(-6) M), a selective blocker of ATP-sensitive potassium channels, caused little or no contraction in rings with or without endothelium. Therefore, in isolated coronary arteries, TEA and 4-AP caused contractions that were independent of the release of vasoactive mediators from the endothelium or perivascular nerves. These effects are not mediated by ATP-sensitive potassium channels or by large and small conductance calcium-activated potassium channels. The data are consistent with an effect of TEA and 4-AP on resting membrane potassium conductance in coronary arteries, resulting in contractions that are sensitive to inhibition by diltiazem. This pattern of responsiveness of isolated coronary arteries to potassium channel blockers differs from that observed in vessels from other vascular beds.

4-Aminopyridine↗
PubMed2000

Structural basis for the biological activity of dendrotoxin-I, a potent potassium channel blocker.

A topochemical model to explain the biological activity of dendrotoxin-I (DTX-I), a potent blocker for potassium channels, was developed by searching common spatial arrangements of functionally important residues between DTX-I, alpha-dendrotoxin, dendrotoxin-K, BgK, ShK, and charybdotoxin. The first three are structurally and functionally related to one another, and specifically target to Kv1 type potassium channels. The last three are structurally unrelated to the first three but have the ability to displace (125)I-labeled dendrotoxins on the same types of potassium channels. In order to obtain the correct electronic surface potential, thought to be crucial for the DTX-I function, we determined the three-dimensional solution structure of DTX-I by nmr spectroscopy using its correct amino acid sequence recently determined by our group. The most interesting characteristic of our model is that DTX-I has two binding sites to potassium channels: one is the cationic domain made up of Lys residues at positions 5 in the 3(10)-helix, 28 and 29 in the beta-turn, and the other is the Lys19/Tyr17/Trp37 triad located in the antiprotease domain. The cationic domain and the triad are located at the opposite sides of the molecular structure and are separated by about 25 A between Lys29 Calpha and Tyr17 Calpha. The functional triad is characterized by three distances, d(1) approximately 7.5 A (Lys19 Calpha-the center of the Tyr17 aromatic ring), d(2) approximately 8.1 A (Lys19 Calpha-the center of the 6-membered ring of the Trp37 indole group), and d(3) approximately 7. 3 A (the center of the Tyr17 aromatic ring-the center of the 6-membered ring of the Trp37 indole group). This model should aid in the pharmaceutical design of peptide and nonpeptide drugs with potassium channel blocking potencies, as well as in understanding of the physiology, pharmacology, biochemistry, and structure-function analysis of potassium channels.

Amino Acid Sequence↗
PubMed1988

Stage-specific distinctions in potassium channel blocker control of T-lymphocyte activation.

Effects of four known blockers of T-lymphocyte potassium channels [verapamil, quinine, 4-aminopyridine (4-AP) and tetraethylammonium (TEA)], were studied on polyclonal T-cell activation induced by two plant mitogens (phytohemmaglutinin; PHA and concanavalin A; ConA), a mitogenic anti-Thy 1.2 monoclonal antibody (mAb G7) and phorbol ester (phorbol myristate acetate; PMA). Potassium channel blockers blocked all four modes of T-cell activation in a dose-dependent fashion with the same rank order of potency (verapamil greater than quinine greater than 4-AP greater than TEA). Kinetic studies of the timing of potassium channel blocker effect, indicated that, while 4-AP and TEA interfere only with early events of T-cell activation, verapamil and quinine can also interfere with later steps of T-cell mitogenesis. This notion was confirmed by studies of interleukin 2(IL-2)-directed activated T-cell growth. Verapamil and quinine blocked this late step in different types of activated T-cells with the same potency they blocked induction of resting T-cell mitogenesis. On the other hand, 4-AP and TEA, at maximal inhibitory doses for resting T-cells, showed little or no effect at IL-2-directed growth. Kinetic studies of the timing of quinine effect showed that the target of quinine action on activated T-cells is critically involved in IL-2 signalling within the first 2-4 h of IL-2 addition. These studies suggest that, besides the voltage-gated potassium channel previously described, a second target for verapamil and quinine action controls IL-2-derived signals to activated T-cells.

4-Aminopyridine↗
PubMed2003

Potassium channel blockers tetraethylammonium and 4-aminopyridine fail to prevent microglial activation induced by elevated potassium concentration.

The effect of potassium channel blocker tetraethylammonium and 4-aminopyridine was examined on the elevated K+ concentration-induced microglial activation on rat hippocampal slice preparations. Microglial cells were detected by immunohistochemisty with a monoclonal antibody (OX 42) raised against a type 3 complement receptor. During activation the morphology of the microglial cells changes and the staining intensity increases. The degree of microglial activation was determined by measuring the integrated optical density of the cells. Tetraethylammonium and 4-aminopyridine failed to reduce the elevated K+ concentration-induced microglial activation. Both potassium channel blockers, when applied on the hippocampal slices without K+, caused significantly increased microglial activation as compared to the control slices. In order to check whether the functional alteration of the neuronal population induced by 4-aminopyridine caused the activation of the microglial cells, Schaffer collaterals were cut to block spreading of epileptiform hyperactivity of the CA3 pyramidal cells to the CA1 region. No significant differences were found in microglial activation between the CA3 and CA1 regions, indicating that the effect of 4-aminopyridine on microglial cells is independent of the epileptiform activity caused by the drug.

4-Aminopyridine↗
PubMed1989

Effect of calcium on synaptic facilitation by potassium channel blockers in superior cervical ganglion of rat.

The effects of potassium channel blockers on synaptic transmission were studied in the isolated superior cervical ganglia of the rat by means of extracellular recordings. The ganglia were exposed to gradual increase in the concentration of calcium in the presence and absence of potassium channel blockers. At all levels of calcium (0.1-2 mM), 4-aminopyridine (4-AP) produced marked potentiation of both amplitude and duration of the compound action potential. At 0.1 mM, 4-AP completely reversed the failure of transmission regularly seen in low calcium (0.1 mM). The increase in duration, measured as time to peak, was more pronounced in low calcium and became less marked as the concentration of calcium was raised. In media containing low concentrations of calcium (0.8 mM), 4-AP induced a massive spontaneous discharge, often with rhythmic bursts. Cesium (6 mM) abolished the action potential in low calcium media, however, increasing levels of calcium in the presence of cesium resulted in recovery and later marked potentiation of both the amplitude and duration of the action potential in a calcium concentration-dependent manner. Guanidine potentiated the amplitude of the compound action potential but had no measurable effect on its duration and was unable to reverse transmission failure in low calcium. No potentiation of the amplitude or duration of the action potential was seen with tetraethylammonium. Neither guanidine nor tetraethylammonium induced a spontaneous discharge. The results suggest that some actions of 4-AP are unrelated to blockade of potassium channels.

4-Aminopyridine↗
PubMed2005

Predictive models for hERG potassium channel blockers.

We report here a general method for the prediction of hERG potassium channel blockers using computational models generated from correlation analyses of a large dataset and pharmacophore-based GRIND descriptors. These 3D-QSAR models are compared favorably with other traditional and chemometric based HQSAR methods.

Anti-Arrhythmia Agents↗
PubMed2003

Inhibitory effects of potassium channel blockers on carbachol-induced contraction in rat detrusor muscle.

We present accidental findings that potassium channel blockers, such as tetraethyl-ammonium (TEA) or 4-aminopyridine (4-AP), inhibit the sustained tonic contraction induced by carbachol in rat detrusor muscle strips. The relatively lower concentrations (<2 mM) of TEA and 4-AP inhibited phasic and tonic contractions induced by 5 micro M carbachol, whilst the relatively higher concentrations of TEA and 4-AP (>5 mM) potentiated phasic contractions. The potentiation of phasic contraction was not observed in nicardipine pretreated condition. In nicardipine pretreated condition, the concentration-response curves for the negative inotropic effect of potassium channel blockers were shifted to the right by the increasing concentration of carbachol from 0.5 microM to 5 microM. IC50 was changed significantly from 0.19 to 0.64 mM (TEA) and from 0.21 to 0.96 (4-AP). Such inhibitory effects were also observed in Ca2+ depleted condition, where 0.1 mM EGTA and 1 microM thapsigargin were added into Ca2+ free solution. In conclusion, inhibitory effects of potassium channel blockers on carbachol-induced contraction may be ascribed to the direct inhibition of receptor-agonist binding.

4-Aminopyridine↗
PubMed2000

Arrhythmogenic activity of cardiac muscle in pulmonary veins of the dog: implication for the genesis of atrial fibrillation.

OBJECTIVE: Pulmonary veins are important foci of ectopic beats to initiate paroxysmal atrial fibrillation. The purpose of this study were to investigate the electrophysiological characteristics of excitable cells in canine pulmonary veins obtained from healthy and chronic rapid atrial pacing dogs and their responses to cardioactive agents. METHODS: Transmembrane action potentials (APs) were recorded from multiple sites of pulmonary veins isolated from 17 healthy dogs and 14 dogs with chronic (6-8 weeks) rapid atrial pacing (780 bpm). RESULTS: In normal superfusate, several types of electrical activities were identified, including silent electrical activity, fast response APs driven by electrical stimulation, and spontaneous fast or slow response APs (with or without early afterdepolarizations). The incidences of AP with an early afterdepolarization (93% versus 41%) was greater in chronic pacing dogs. The spontaneous activities were depressed by beta-adrenoceptor blocker, calcium channel blocker, adenosine and acetylcholine. High frequency (>8 Hz) irregular rhythms occurred spontaneously or were induced by cardioactive agents or electrical stimuli. The incidence of spontaneously occurring tachyarrhythmias was much higher in preparations from chronic pacing dogs (93%) than from control (12%). The tachyarrhythmias were suppressed by sodium channel blocker, potassium channel blocker or magnesium. CONCLUSIONS: Pulmonary veins have arrhythmogenic ability through spontaneous activities or high-frequency irregular rhythms. The higher incidence of spontaneously occurring high-frequency irregular rhythms in chronic rapid atrial pacing dogs may account for the increased risk of atrial fibrillation in these dogs.

Acetylcholine↗
PubMed2003

Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing.

Potassium ion (K(+)) channels are attractive targets for rational drug design. Based upon a three-dimensional model of the eukaryotic K(+) channels, the docking virtual screening approach was employed to search the China Natural Products Database. Compounds were ranked according to the relative binding energy, favorable shape complementarity, and potential of forming hydrogen bonds with the K(+) channel. Four candidate compounds found by virtual screening were investigated by using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. When applied extracellularly, compound 1 markedly depressed the delayed rectifier K(+) current (I(K)) and fast transient K(+) current (I(A)), whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory effect on I(K). Intracellular application of the four compounds had no effect on both the K(+) currents.

Animals↗
PubMed2005

[Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline].

Anisodamine, which is originally extracted from scopolia tangutica and is currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K(+)-evoked contraction of rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA)-, histamine- or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K(+)-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilation effect of some potassium channel activators may be inhibited or abolished in high K(+) solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channel blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3 and 10 micromol/L of anisodamine, significantly relaxed the 0.01 micromol/L NA precontracted aortic ring by (19.1+/-3.1)%, (30.1+/-3.8)% and (38.3+/-4.2)%, respectively, compared with the controls [by (4.8+/-2.4)%, (5.1+/-1.8)% and (5.6+/-2.5)%, respectively] (P<0.01). 10 mmol/L of CsCl (a non-selective potassium channel blocker), 1 mmol/L of 4-aminopyridine [a selective voltage-activated potassium channel (K(V)) blocker], 10 mumol/L BaCl2 (a selective inwardly-rectifying potassium channel blocker), 10 micromol/L of glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 micromol/L of charybdotoxin (a large- and intermediate-conductance Ca(2+)-activated potassium channels blocker) and 3 micromol/L of apamin (a selective small conductance Ca(2+)-activated potassium channel blocker) significantly increased the NA-induced contraction by (14.4+/-3.2)%, (16.3+/-5.8)%, (12.7+/-4.2)%, (13.6+/-2.0)%, (11.1+/-5.5)% and (13.4+/-4.3)%, respectively, compared with the control [by (5.6 +/-1.2)%] (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxation of the 0.01 micromol/L NA contracted rabbit aortic rings [(28.8+/-3.0)% and (15.9+/-3.7)% or (29.7+/-3.9)% and (19.0+/-5.0)%] significantly deceased, compared with that in the absence of any potassium channel blocker [(38.3+/-4.2)% (P<0.01)] in a 8-min period. However, in the presence of 10, 30 micromol/L of BaCl2, 10, 30 micromol/L of glibenclamide, 3 micromol/L of charybdotoxin, or 3 micromol/L apamin, 10 micromol/L anisodamine-induced relaxation [(37.1+/-3.8)%, (36.2+/-4.7)%, (36.1+/-2.7)%, (35.6+/-3.3)%, (37.8+/-2.0)% and (39.3 +/-4.7) %, respectively] did not decrease, compared with the control [(38.3+/-4.2)%] (P>0.05). This study suggests that K(V) blockers inhibit anisodamine-induced relaxation of the rabbit aortic smooth muscle precontracted with NA and implies that the K(V) in VSMC membrane plays a role in anisodamine-induced relaxation of blood vessels.

Animals↗
PubMed1991

Effects of some potassium channel blockers on the ionic currents in myelinated nerve.

The effects of some potassium channel blockers on the ionic currents and on the so-called K(+)-depolarization in intact myelinated nerve fibres were studied. 4-AP, and in particular, Flaxedil, proved to be selective K(+)-current blockers. However, TEA, a crown ether (DCH18C6), a longchained triethylammonium compound (C10-TriEA), capsaicin, and the extract from the medicinal herb Ruta graveolens proved not to be selective K(+)-current blockers; they all block Na(+)-currents as well, although to a lesser extent. The sodium inactivation curve did not change under TEA and Flaxedil but was shifted on the potential axis in negative direction by DCH18C6, 4-AP, capsaicin and the Ruta extract whereas C10-TriEA caused a shift of both sodium inactivation and activation parameters in positive direction. Regarding to the kinetics of the persisting K(+)-current fraction, two different kinds of blockade were found: 1. Unchanged K(+)-kinetic which is typical for the effects of TEA, 4-AP, Flaxedil, and C10-TriEA. 2. Clearly changed K(+)-kinetic, characterized by K(+)-transients; which is typical for the effects of capsaicin and in particular, for those of DCH18C6 and of the Ruta extract. The possibly different modes of action of both groups of blockers are discussed in terms of current models for the action of potassium channel blockers.

4-Aminopyridine↗
PubMedDate not supplied

Sensitivity of the slow component of the delayed rectifier potassium current (IKs) to potassium channel blockers: implications for clinical reverse use-dependent effects.

The slow delayed rectifier potassium current (I(Ks)) is unique in its slow activation and deactivation kinetics. It is important during cardiac repolarization, especially when the heart rate is fast. We compared the effects of quinidine, procainamide, sotalol, and amiodarone on I(Ks) and correlated the findings with the clinical reverse use-dependent effects of potassium channel blockers. Human minK RNA was obtained by reverse transcription-polymerase chain reaction using explanted human heart. The RNA was injected into Xenopus oocytes for heterologous expression of I(Ks). A two-electrode voltage clamp technique was performed to investigate the I(Ks). We demonstrated that quinidine, sotalol and procainamide had no effects on I(Ks) up to a concentration of 300 microM while amiodarone inhibited I(Ks) in a concentration-dependent manner starting from 10 microM. The inhibition by amiodarone was state-dependent with gradual unblocking after depolarization. The degree of inhibition was 53% immediately after depolarization and 19% at the end of a 5-second depolarization. I(Ks) is 30 times more sensitive to amiodarone than to quinidine, sotalol, and procainamide. Quinidine, sotalol and procainamide have reverse use-dependent effects while amiodarone does not. This is compatible with the hypothesis that no inhibition of I(Ks) at clinical concentrations contributes to the clinical reverse use-dependent effects.

Amiodarone↗
PubMed1991

Potassium channel blockers: could they work in Alzheimer disease?

Many of the actions of potassium channel blockers, such as 4-aminopyridine, appear to complement the deficits in Alzheimer disease. The two clinical studies in the literature are contradictory, so potassium channel blockers may still merit trial in Alzheimer disease.

4-Aminopyridine↗
PubMed2004

The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.

Predictive pharmacophore models were developed for a large series of I(Kr) potassium channel blockers as class III antiarrhythmic agents using HypoGen in Catalyst software. The pharmacophore hypotheses were generated using a training set consisting of 34 compounds carefully selected from documents. Their biological data, expressed as IC(50), spanned from 1.5 nM to 2.8 mM with 7 orders difference. The most predictive hypothesis (Hypo1), consisting of four features (one positive ionizable feature, two aromatic rings and one hydrophobic group), had a best correlation coefficient of 0.825, a lowest rms deviation of 1.612, and a highest cost difference (null cost-total cost) of 77.552, which represents a true correlation and a good predictivity. The hypothesis Hypo1 was then validated by a test set consisting of 21 compounds and by a cross-validation of 95% confidence level with randomizing the data using CatScramble program. Accordingly, our model has strong predictivity to identify structural diverse I(Kr) potassium channel blockers with desired biological activity by virtual screening

Anti-Arrhythmia Agents↗