Landiolol (Onoact) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.

Adaprolol is a beta-adrenergic antagonist that is being developed as a topical agent to treat glaucoma. Adaprolol demonstrated a safer cardiovascular profile, especially in the population over 70 years old. It was in Phase II clinical trials for the treatment of glaucoma. This research has been discontinued.

Corydaline is a pharmacologically active isoquinoline alkaloid isolated from Corydalis tubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. Corydaline exhibited strong nematocidal activity, showed little cytotoxicity and represents a potential treatment for Strongyloidiasis. Corydaline exhibits gastrointestinal modulatory, antinociceptive, anti-allergic, and anti-parasitic activities. Corydaline is currently in clinical trials as a potential treatment for functional dyspepsia. In animal models, corydaline increases gastric emptying and small intestine transit speed and induces gastric relaxation. In other animal models, corydaline inhibits chemically-induced pain. Additionally, this compound may inhibit mast cell-dependent smooth muscle contraction of the aorta. Corydaline also exhibits nematocidal activity against species of Strongyloides.

Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It has inhibitory effects on both the slow calcium and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. It is used to treat hypertension (high blood pressure), angina (chest pain), sustained atrial fibrillation and tachyarrhythmia. The most common side effects were upper gastrointestinal complaints (nausea, dyspepsia or GI distress), diarrhea, dizziness, asthenia and nervousness. Certain drugs could increase the likelihood of potentially serious adverse effects with bepridil hydrochloride. In general, these are drugs that have one or more pharmacologic activities similar to bepridil hydrochloride, including anti-arrhythmic agents such as quinidine and procainamide, cardiac glycosides and tricyclic anti-depressants. Anti-arrhythmics and tricyclic anti-depressants could exaggerate the prolongation of the QT interval observed with bepridil hydrochloride. Cardiac glycosides could exaggerate the depression of AV nodal conduction observed with bepridil hydrochloride.

Bepridil (trade name Vascor) is an amine calcium channel blocker used to treat angina. Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride. Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works. Bepridil is no longer sold in the United States, but it is still marketed in other countries. Bepridil has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. Although, it contains one chiral center, it is generally administered as a racemates. The drug bepridil is a racemic mixture of two enantiomers for the 2R as CID 16048570 and 2S as CID 445143. (R)-isomer of bepridil is more active than (-S)- isomer, in certain cases. In the retrogradely perfused, paced rat heart the higher activity was found for the ( )-enantiomer, which was 4.27 times more potent in increasing coronary flow than the (-)-isomer. The two enantiomers of bepridil showed a lower activity on maximum systolic left ventricular pressure (MSLVP) than on coronary flow, and a similar 3-4 fold stereoselectivity with both parameters.

Bepridil (trade name Vascor) is an amine calcium channel blocker used to treat angina. Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride. Bepridil has inhibitory effects on both the slow calcium (L-type) and fast sodium inward currents in myocardial and vascular smooth muscle, interferes with calcium binding to calmodulin, and blocks both voltage and receptor operated calcium channels. Bepridil inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. This has been demonstrated in isolated myocardial and vascular smooth muscle preparations in which both the slope of the calcium dose response curve and the maximum calcium-induced inotropic response were significantly reduced by bepridil. In cardiac myocytes in vitro, bepridil was shown to be tightly bound to actin. Bepridil regularly reduces heart rate and arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing total peripheral resistance (afterload) against which the heart works. Bepridil is no longer sold in the United States, but it is still marketed in other countries. Bepridil has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. Although, it contains one chiral center, it is generally administered as a racemates. The drug bepridil is a racemic mixture of two enantiomers for the 2R as CID 16048570 and 2S as CID 445143. (R)-isomer of bepridil is more active than (-S)- isomer, in certain cases. In the retrogradely perfused, paced rat heart the higher activity was found for the ( )-enantiomer, which was 4.27 times more potent in increasing coronary flow than the (-)-isomer. The two enantiomers of bepridil showed a lower activity on maximum systolic left ventricular pressure (MSLVP) than on coronary flow, and a similar 3-4 fold stereoselectivity with both parameters.

Pilsicainide is marketed in Japan as (Sunrythm). Pilsicainide controls the cardiac conduction abnormalities and improves the symptoms of arrhythmia with the blocking action on Na channel. It is usually used to treat tachycardiac arrhythmia. Pilsicainide did not affect the resting membrane potential. Under the voltage-clamp condition, pilsicainide inhibited the transient outward current (Ito) that is more prominent in the atrium than in the ventricle in a concentration-dependent manner. However, in contrast to other class Ic agents, the inhibition to Ito by pilsicainide was observed only at much higher concentrations (IC50-300 uM) and did not affect the inactivation time-course of Ito. Moreover, the drug (10 uM) did not significantly affect the Ca2+, delayed rectifier K+, inward rectifying K+, acetylcholine-induced K+ or ATP-sensitive K+ currents. From these results pilsicainide could be differentiated as a pure Na+ channel blocker from other class Ic agents with diverse effects on membrane currents and should be recognized accordingly in clinical situations. A single oral dose of pilsicainide effectively restores normal sinus rhythm in patients with recent-onset atrial fibrillation and a healthy left ventricle. Long-term therapy with pilsicainide is successful in treating chronic atrial fibrillation

Landiolol (Onoact) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.

Adaprolol is a beta-adrenergic antagonist that is being developed as a topical agent to treat glaucoma. Adaprolol demonstrated a safer cardiovascular profile, especially in the population over 70 years old. It was in Phase II clinical trials for the treatment of glaucoma. This research has been discontinued.

Corydaline is a pharmacologically active isoquinoline alkaloid isolated from Corydalis tubers. It exhibits the antiacetylcholinesterase, antiallergic, antinociceptive, and gastric emptying activities. Corydaline exhibited strong nematocidal activity, showed little cytotoxicity and represents a potential treatment for Strongyloidiasis. Corydaline exhibits gastrointestinal modulatory, antinociceptive, anti-allergic, and anti-parasitic activities. Corydaline is currently in clinical trials as a potential treatment for functional dyspepsia. In animal models, corydaline increases gastric emptying and small intestine transit speed and induces gastric relaxation. In other animal models, corydaline inhibits chemically-induced pain. Additionally, this compound may inhibit mast cell-dependent smooth muscle contraction of the aorta. Corydaline also exhibits nematocidal activity against species of Strongyloides.