Verapamil is a FDA approved drug used to treat high blood pressure and to control chest pain. Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias. Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.

Spironolactone is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. Due to its anti-androgen effect, it can also be used to treat hirsutism, and is a common component in hormone therapy for male-to-female transgendered people. Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly. Spironolactone is a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents which act more proximally in the renal tubule. Aldosterone interacts with a cytoplasmic mineralocorticoid receptor to enhance the expression of the Na+, K+-ATPase and the Na+ channel involved in a Na+ K+ transport in the distal tubule . Spironolactone bind to this mineralcorticoid receptor, blocking the actions of aldosterone on gene expression. Aldosterone is a hormone; its primary function is to retain sodium and excrete potassium in the kidneys. Spironolactone is used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.

Rostafuroxin (PST 2238) is a digitoxygenin derivative, which selectively displaces ouabain from the Na ,K -ATPase receptor. PST 2238, at concentrations up to 10−4 M, did not show any significant interaction with a- and b-adrenergic, D1, D2, D3, 5-HT1, 5-HT2, H1, H2, M1, M2, A1, A2, Ca2 , Na , or K channel–associated receptors, AT1, AT2, ETa, ETb, GABA, thromboxane, vasopressin, angiotensin II, or the steorid-hormone receptors (androgen, progestogen, estrogen and mineralocorticoid), confirming that PST 2238 is specific for Na ,K -ATPase. Rostafuroxin has been developed in an attempt to unravel the contribution of mutated adducin and endogenous ouabain in the pathogenesis of hypertension. The compound lowered blood pressure in Milan hypertensive rats and humans. Rostafuroxine had been in phase II clinical trials for the treatment of hypertension. Following adverse events in Rostafuroxin group were described: dizziness, headache, upper respiratory tract infections, high blood pressure.

The new chemical entity KC12615 is a potent f neutral endopeptidase inhibitor with additional endothelin-converting enzyme (ECE)–inhibitory activity.2 KC12615 is the hydrolyzed form of the oral prodrug SLV306 (daglutril). In plasma, the compound increases natriuretic peptide levels and prevents the formation of endothelin-1 by inhibiting the degradation of its precursor, big endothelin. It is investigated for use/treatment in congestive heart failure and hypertension.

Lercanidipine is antihypertensive drugs which acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. Lercanidipine exists as a racemate, with anti-hypertensive activity residing primarily in S-enantiomer. NDA for lercanidipine was submitted to FDA in 2002 by Forest Laboratories, but FDA refused to approve the drug, and lercanidipine is not marketed in USA. Lercanidipine is also investigated in preclinical models of epilepsy and ischemic stroke.

(R)-Lercanidipine is enantiomer of antihypertensive drugs Lercanidipine, that acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. The dihydropyridine calcium antagonists promote systemic vasodilatation by a reversible blockade of voltagedependent Ca2+ influx through L-type channels in the cell membrane. (S)-Lercanidipine has 100- to 200-fold greater affinity than the (R)-enantiomer for the L-type calcium channel. The pharmacokinectics of (S)- Lercanidipine has been evaluated in healthy volunteers, in elderly and non-elderly patients with hypertension, and in patients with renal or hepatic impairment. Patients from these studies were investigated after receiving a single 10 or 20 mgdose of [14C]-labeled rac-Lercanidipine as a solution. The maximum plasma concentrations of (S)-Lercanidipine were reached within 2–3 h and the area under the plasma concentration–time curves were not linearly related to the dose, indicating a saturable first-pass metabolism. The absorption of (S)-LER increases after the ingestion of a highfat meal. Lercanidipine is highly bound to plasma protein (>98%) in humans. Its volume of distribution of 2–2.5 L/kg was determined in healthy volunteers after intravenous infusion of 2 mg. Lercanidipine is extensively metabolized by CYP 3A4 to inactive pyridine derivatives. A crossover study involving a single administration of either 10 mg of (R)- or (S)-LER or 20 mg of rac-LER as a solution demonstrated no in vivo enantiomer interconversion

(S)-Lercanidipine is enantiomer of antihypertensive drugs Lercanidipine, that acts by blocking L-type calcium channels, allowing relaxation and opening of blood vessels. The dihydropyridine calcium antagonists promote systemic vasodilatation by a reversible blockade of voltage-dependent Ca2+ influx through L-type channels in the cell membrane. (S)-Lercanidipine has 100- to 200-fold greater affinity than the (R)-enantiomer for the L-type calcium channel. The pharmacokinetics of (S)- Lercanidipine has been evaluated in healthy volunteers, in elderly and non-elderly patients with hypertension, and in patients with renal or hepatic impairment. Patients from these studies were investigated after receiving a single 10 or 20 mg dose of [14C]-labeled rac-Lercanidipine as a solution. The maximum plasma concentrations of (S)-Lercanidipine were reached within 2–3 h and the area under the plasma concentration-time curves were not linearly related to the dose, indicating a saturable first-pass metabolism. The absorption of (S)-LER increases after the ingestion of a high-fat meal. Lercanidipine is highly bound to plasma protein (>98%) in humans. Its volume of distribution of 2–2.5 L/kg was determined in healthy volunteers after intravenous infusion of 2 mg. Lercanidipine is extensively metabolized by CYP 3A4 to inactive pyridine derivatives. A crossover study involving a single administration of either 10 mg of (R)- or (S)-LER or 20 mg of rac-LER as a solution demonstrated no in vivo enantiomer interconversion

Fimasartan is a angiotensin II receptor antagonist which was developed in Korea for the treatment of hypertension. The drug is available in different forms: Kanarb, Dukarb (in combination with Amlodipine), Tuvero (in combination with Rosuvastatin). Fimasartan was tested to be effective in Mexican and Russian population and now is being tested in the USA.

Nilvadipine (NIVADIL®) is a L-type calcium channel blocker for treatment of hypertension. It inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Tripamide is a new diuretic derived from a sulfonamide nucleus that has both antihypertensive and natriuretic properties. It is Na-K-Cl cotransporter inhibitor. The antihypertensive mechanism of tripamide is considered to be based on a mild saluretic action and a peripheral vasodilation action. Tripamide is an ingredient of Normonal in Japan, indicated for the treatment of essential hypertension.